18. The most popular halogen substitutions are the less reactive aromatic flurorine and chlorine groups. Othe aliphatic C-halgen bonds are weaker and so more reactive (b)CF3. It is approximately the same size as a chlorine atom 9. Bioisostere: Analogues can also be formed by replacing an existing substituent in the structure of a lead by a new substituent group Pharmacophore: The important functional groups that are required for binding or activity, and their relative positions in space (a) Sulphonic acid groups do not usually have any effect on the biological activity but will increase the rate of excretion of an analogue (b)Methyl groups usually increases the lipophilicity of the compound and reduces its water solubility as shown by an increase in the value of the partition coefficient (c)Thiol are not usually introduced into leads in SAR studies because they are readily metabolized by oxidation 21. QSAR is an attempt to remove this element of luck from drug design by establishing mathematical relationship in the form of an equation between biological activity and measurable physicochemical parameters. These parameters are used to represent properties such as lipophilicity, shape and electron distribution, which are believed to have a major influence on the drugs activity. They are normally defined so that they are in the form of numbers derived from practical data that are thought to be related to the property that the parameters represents 22. A: Lipophilicity: P(Partition coefficients), I(Lipophilic substituent constants), D(Distribution Coefficient) Shape: Es(The Taft steric parameter)and MR(Molar refractivity) Electronic effects: o(The Hammett constant) 23. advantages: less computing time, very large molecules may be modeled and can be used to give information on the binding of ligands to the target site. Disadvantages: accuracy of the structure depends on selecting the correct force field and parameter values. Structures are normally determined at zero Kelvin so they will have different conformations at room and bod 24. Local minimum energy conformations are the nearest conformation of local minimum energy from the starting conformation Global minimum energy conformations are the lowest conformation of global minimum energy thus is one kind of local minimum energy Though the global is not necessary the active conformation, it is also considered as the active conformation since the active conformation is one certain minimum energy conformation. 25. Molecular dynamics: show the dynamic nature of molecules by simulating the natural motion of the atoms in a structure18. The most popular halogen substitutions are the less reactive aromatic flurorine and chlorine groups. Othe aliphatic C-halgen bonds are weaker and so more reactive. (b) CF3. It is approximately the same size as a chlorine atom. 19. Bioisostere: Analogues can also be formed by replacing an existing substituent in the structure of a lead by a new substituent group. Pharmacophore: The important functional groups that are required for binding or activity, and their relative positions in space. 20. (a) Sulphonic acid groups do not usually have any effect on the biological activity but will increase the rate of excretion of an analogue. (b) Methyl groups usually increases the lipophilicity of the compound and reduces its water solubility as shown by an increase in the value of the partition coefficient. (c) Thiol are not usually introduced into leads in SAR studies because they are readily metabolized by oxidation. 21. QSAR is an attempt to remove this element of luck from drug design by establishing a mathematical relationship in the form of an equation between biological activity and measurable physicochemical parameters. These parameters are used to represent properties such as lipophilicity, shape and electron distribution, which are believed to have a major influence on the drug’s activity. They are normally defined so that they are in the form of numbers derived from practical data that are thought to be related to the property that the parameters represents. 22. A: Lipophilicity: P(Partition coefficients), π(Lipophilic substituent constants),D(Distribution Coefficient) Shape: Es (The Taft steric parameter) and MR (Molar refractivity) Electronic effects: σ(The Hammett constant) 23. advantages: less computing time, very large molecules may be modeled and can be used to give information on the binding of ligands to the target site. Disadvantages: accuracy of the structure depends on selecting the correct force field and parameter values. Structures are normally determined at zero Kelvin so they will have different conformations at room and body temperatures. 24. Local minimum energy conformations are the nearest conformation of local minimum energy from the starting conformation. Global minimum energy conformations are the lowest conformation of global minimum energy, thus is one kind of local minimum energy. Though the global is not necessary the active conformation, it is also considered as the active conformation since the active conformation is one certain minimum energy conformation. 25. Molecular dynamics: show the dynamic nature of molecules by simulating the natural motion of the atoms in a structure