Exploration of Novel Chemical Space: Synthesis and in vitro Evaluation of N‐Functionalized Tertiary Sulfonimidamides

• Published in: Chemistry : a European journal Vol. 24; no. 37; pp. 9295 - 9304
• Main Authors: Izzo, Flavia, Schäfer, Martina, Lienau, Philip, Ganzer, Ursula, Stockman, Robert, Lücking, Ulrich
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.07.2018; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Alkylation; Chemical compounds; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; drug design; medicinal chemistry; Molecular chains; N-functionalization; Organic chemistry; Physical Sciences; Reaction products; Science & Technology; structural diversity; sulfonimidamides; Urea; SULFOXIMINES; BAY 1143572; drug design; structural diversity; ONE-POT; DRUG DISCOVERY; sulfonimidamides; UNPROTECTED SULFONIMIDAMIDES; BORONIC ACIDS; ELECTROPHILIC NH; SULFUR-COMPOUNDS; INHIBITOR; N-functionalization; medicinal chemistry
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201801557

An unprecedented set of structurally diverse sulfonimidamides (47 compounds) has been prepared by various N‐functionalization reactions of tertiary =NH sulfonimidamide 2 aa. These N‐functionalization reactions of model compound 2 aa include arylation, alkylation, trifluoromethylation, cyanation, sulfonylation, alkoxycarbonylation (carbamate formation) and aminocarbonylation (urea formation). Small molecule X‐ray analyses of selected N‐functionalized products are reported. To gain further insight into the properties of sulfonimidamides relevant to medicinal chemistry, a variety of structurally diverse reaction products were tested in selected in vitro assays. The described N‐functionalization reactions provide a short and efficient approach to structurally diverse sulfonimidamides which have been the subject of recent, growing interest in the life sciences. An unprecedented set of structurally diverse sulfonimidamides has been prepared by various N‐functionalization reactions. In vitro studies did not reveal any intrinsic flaw of the sulfonimidamide group regarding properties relevant to medicinal chemistry.