The research progress of sulfonimidamide

As a kind of rich jnd import ant pharmaceutical motify, sulfamide widely exits in medicine and shows superior biological activities, such as anticancer, anti-inflammatory, antiviral, antihypertensive, hypoglycemic etc. According to the latest report, sulfamide skeleton accounts for 29_ of sulfur-containing drugs. When an oxygen atom in the sulfonamide is replaced by a nitrogen atom, these jzj jnjlogues jre cjlled sulfonimidjmides. 8ulfonimidjmides jre the jnjlogues of aza-sul-fonami des. They have a h i gh stab i i i ty, good phys i ca! and chem i cal propert i es, structural d ivers i t i es and hydrogen bond receptors and donors, which are simllar with sulfoximine. The change of the substituents on nitrogen can regulate the biological activity and physicochemical properties of the compounds. Therefore, pharmaceutical chemists have employed sulfonimidamides to the optimization of lead compounds instead of sulfonamides or carboxylic acids, and found that their structures have better activity and different configurations play different roles. In ths review, the properties and synthes is methods of sulfoni m i dam i des were summar i zed. The synthes is strateg ies of sulfon i m i dam i des were mainly divided into racemic sulfonimidamides and chiral sulfonimidamides. Meanwhlle, the advantages and disadvantages of various synthetic methods of sulfonimidamides were also analyzed and summa-rzed.There are many synthetic methods developed for the synthesis of racemic sulfonimidamide. Accord ing to the i ntermed iates for the synthes is of racem i c sulfoni m i dam i de, the synthet i c methods are divided into chlorosulfonamides, fluorinated sulfonamides, sulfonimide imidazolium salts, sulfonim-i de esters, sulfonami des, sulfinam i de and sulfenami de. Oxd iat i ve i m i dat i on of chlor i nated sulfoxide and nucleophllic substitution of chlorinated intermediate can achieve the synthesis of racemk sulfonimidamide. 8ynthesis of sulfonimidamide via the deoxygenative chloridation of sulfonamide has also been explored. The synthesis of sulfonimidamides can be achieved from 8OF4 in three steps.