Fundamentals of Medicinal Chemistry

4.4.2 Electronic effects The distribution of the electrons in a drug molecule has a considerable influence on the distribution a ...

and so varies with the position of that substituent in the molecule. This variation is indicated by the use of the subscripts m ...

the Taft steric parameter (Es). It was followed by Charton’s steric parameter (n), Verloop’s steric parameters and the molar ref ...

MR¼ (n^2 1)M (n^2 þ2)r (4:9) wherenis the refractive index,Mthe relative mass andrthe density of the compound. TheM/rterm is a ...

Each of these stages is dependent on the chemical and physical properties of the drug and its target site. In Hansch analysis th ...

Table 4.8 Examples of simple Hansch equations Compound Activity Hansch equation CH 3 CH 3 COOH S N OCHCO X (CH 2 )nCH 3 C O X Y ...

for example, a series of analogues whose activity is related to the parametersp andsby the hypothetical Hansch equation: log 1=C ...

analogues. For example, suppose that a Hansch analysis carried out on a series of aromatic compounds yields the Hansch equation: ...

(a) (b) L M L E M E 4 −C(CH 3 ) 3 or 3,4−dimethyl L M 3 −Cl 3 −N(CH 3 ) 2 3 −CH 3 2 −Cl 4 −F 4−NO 2 3 −CF 3 and 3−Br and 3−I 3,5 ...

H Y (A) Cl Cl Cl Cl Cl Y (B) LM E Y (C) LM CF 3 Y (F) (E) (D) O 2 N Y Y E Key : Y = the structure of the rest of the lead compou ...

4.6 Questions (1) State the full wording of the abbreviation ‘SAR’. Describe the general way in which SAR is used to develop a d ...

(continued) (8) (a) How are Craig plots used in Hansch analysis? (b) Use Figure 4.6 to predict the structures of the analogues o ...

...

5 Computer Aided Drug Design 5.1 Introduction The development of powerful desk top and larger computers has enabled chemists to ...

(a)Stick model of aspirin. (b)Space fill model model of aspirin (CPK model) (c)Stick model of Vitamin E. (d)Space fill model mod ...

A (a) (b) x z y Z X Y A Z X Y Coordinates arer,θ and φ. θ φ r Coordinates arex,y and z Figure 5.2 (a) Cartesian and (b) polar co ...

5.1.2 Computer graphics In molecular modelling the data produced are converted into visual images on a computer screen by graphi ...

(a) (b) (c) (d) Figure 5.3 (a) Ball and stick representation of aspirin. (b) Ribbon representation of dihydrofo- late reductase. ...

r 0 r 0 r r Equilibrium bond length Stretched bond length Compressed bond length r 1 r 1 E Figure 5.4 Bond stretching and compre ...

Table 5.1 Some of the expressions commonly used to calculate the energy terms given in equation (5.1) Term Expression Model for ...