利尿药和降血糖药 PPT.ppt

Medicinal chemistry;Chapter 10 Diuretics and Synthetic Hypoglycemic Drugs;Section 1 Hypoglycemic Drugs;Definitions ;Biochemistry and Pathogenesis of Diabetes; Physical-Chemical Properties; Structure-activity Relationships;Many simple substituents on the sulfonyl aromatic ring are active. The p-(β-arylcarboxamidoethyl) grouping seen in second generation compounds is consistent with high potency. It is thought that the spatial relationship between the amide nitrogen of the substituent and the sulfonamide nitrogen is important. ; Tolbutamide; Properties ;Instability: Tolbutamide is hydrolyzed to para-toluene sulfonamide by acids. Heating of its filtrate with sodium hydroxide solution produces n-butylamine odour. ;Metabolism ;Glibenclamide;Properties ;Metabolism;Therapeutic Application;Synthetic Route;Third-generation sulfonylurea; Metformin hydrochloride; Mechanism of Action; Actions and Uses; α- Glucosidase Inhibitors;Metabolism of complex carbohydrades ; Section 2 Diuretics; Structure Classification;Furosemide; Structure-activity Relationships; Therapeutic Applications;Hydrochlorothiazide; Mechanism of Action; Structure-activity Relationship;Saturation of the double bond to give a 3, 4 dihydro derivative produces a diuretic that is 10 times more than the unsaturated derivative. Substitution lipophilic group at position 3 gives a marked in the diuretic potency with a longer duration of action. Alkyl substitution on the 2-N position also decreases the polarity and increases the duration of diuretic action. ;Therapeutic Applications;Acetazolamide;Mechanism of Action;Spironolactone; Mechanism of Action; Metabolism;Canrenone is an antagonist to aldosterone and it has been suggested as the active form of spironolactone. The canrenoate anion is not active per se but acts as aldosterone antagonist because of its conversion to canrenone. The most serious side effect of spironolactone is hyperkalemia because it has a potassium-sparing effect. ; Triamterene; Stru