Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry

Abstract

Sulfoximines have been largely disregarded in medicinal chemistry for a long time. However, recently, they have risen to the apparent level of stardom on the drug discovery scene. Considering the outstanding properties of sulfoximines, this versatile functional group has advanced to implementation in several drug discovery programs. Currently, this fashionable functional group can be found in various hit-to-lead and lead optimization studies in early stages and in several compounds currently in clinical trials. Herein, we review recent developments to demonstrate the scope and limitations of this interesting and versatile functional group in medicinal chemistry and drug discovery.

How do we address neglected sulfur pharmacophores in drug discovery?

“…Only a single agrochemical, the insecticide Sulfoxaflor (7), has reached the market, gaining approval in 2013. Several reports have investigated sulfoximines as potential pharmacophores [9]. In particular, the pharmacokinetics of sulfoximine drug analogues have been explored numerous times.…”

“…However, this approach is limited by the formation of N-substituted sulfoximines, which require further deprotection and functionalisation. In addition, toxic and explosive reagents are required [9]. In recent years, several breakthroughs have been achieved that allow rapid access to free (N-H) sulfoximines, under milder conditions, including the direct oxidation from thioethers (B) [10,11].…”

Rediscovering Sulfinylamines as Reagents for Organic Synthesis

“…This field has been covered in a previous review, [13] but we highlight here a more recent asymmetric example by Gautun and coworkers. [35] Sulfinylamines substituted with Cbz (25) or tosyl (2) groups formed adducts with 1,3-cyclohexadiene in the presence of 10 mol% of chiral bisoxazoline ligand 27 complexed to Cu(OTf) 2 or Zn(OTf) 2 , respectively (Scheme 11). The endo products 26 a and 26 b were obtained selectively in good yields with 98 % and 97 % ee, respectively.…”

What’s in a Name? Drug Nomenclature and Medicinal Chemistry Trends using INN Publications

“…While none of the three SCEs has been approved so far, a recent article pointed at sulfoximine as an emerging group to further expand the toolbox of medicinal chemists. 57 …”