Design, Synthesis And Screening Of Sulfonylureas

Diabetes Mellitus is an increasingly common, serious metabolic disorder with a substantial inherited component. The incidence of diabetes is occurring at an alarming rate with more convenient life and the changes of the life style. The explosive increase in number of people diagnosed with diabetes makes this disease a new health threat.Diabetes Mellitus is a condition characterized by elevated levels of blood glucose, glucosuria, the reduction of glucose tolerance, and the abnormity of insulin release assay. The elevation of glucose may result from either a deficiency of endogenous production of insulin or from resistance to the effects of insulin. It is also a common disorder which is associated with a markedly increased morbidity and mortality rate and is the leading cause of blindness, renal failure, and lower limb amputation. Thus many efforts have been made to find an agent to improve insulin action.Type 2 diabetes is the result of the combined effects of insulin resistance coupled with a relative deficiency of endogenous insulin production. The sulfonylureas may be paramount in their chronic antidiabetic action. A specific site on the adenosine triphosphate(ATP)-sensitive potassium channels is occupied by sulfonylureas leading to closure of the potassium channels and subsequent opening of cacium channels, which triggers insulin release from the pancreatic β cell.The paper includes the several works illustrated below:1. We choose ATP-sensitive K+ channels as the target of new type of antihyperglycemic drugs. According to the proposed mechanism of sulfonylureas and structure characteristics, we designed new lead optimization compounds. Four types of sulfonylureas were designed with four substitutions on template, and the structure of 19 compounds have been synthesized and identified. The building blocks consist of sulfonamides and amines.2. Three synthetics were employed here for the synthesis of the different structural of sulfonylurea compounds by which the common intermediates can be made good use of. All of the reaction conditions are moderate, timesaving and easy to workup which is suitable for the large scale synthesis. The building blocks are facile,...