药物化学构效关系（Structure-activity relationship）.docVIP

药物化学构效关系（Structure-activity relationship） Barbiturates Barbiturates are structural nonspecific drugs Nonspecific drugs: the biological activity of drugs has little to do with the chemical structure of drugs, and is related to the physical and chemical properties Structural specific drugs: the effects of drugs depend on the specific chemical structure and spatial arrangement of the drug molecules The effect of barbiturates and the time of onset of action are closely related to the dissociation constant of drugs, PKa, and the partition coefficient of lipid water Dissociation constant: a drug acts as a molecular form through a biological membrane and acts as an ionic form Oil-water partition coefficient: the drug can transport both in the body fluid and the blood brain barrier The 5 drugs have two substituents to have activity, when the two substituents, the total number of carbon atoms between 4 to 8, the best distribution coefficient of moderate activity. When the total number of carbon atoms is more than 8 when the effect is too strong, easy to produce convulsion effects. In the structure of the N atom on the imide a methyl substituted can reduce acidity and increase fat soluble, more quickly. S is replaced with C-2 bit O. The fat soluble, easily through the blood-brain barrier, more quickly. The metabolism process of barbiturates is related to the time of metabolism of drugs Two. Two benzodiazepines (diazepam) The A ring is necessary for the activity, and the.B ring can be replaced by other aromatic heterocycles, but still retains its activity The 1 is usually N-CH3.-CH3, but can be removed from metabolism, but still retains its activity The 1.2 bit parallel into heterocyclic (three midazolam: stability increased activity increased) The 3 atom, a H atom, can be replaced by -OH, but its activity is slightly reduced, but its toxicity is very low 4,5 is a double bond and is saturated. Activity is reduced and incorporated into the ring to increase sedation and antidepr