Synthesis and Functionalization of Cyclic Sulfonimidamides: A Novel Chiral Heterocyclic Carboxylic Acid Bioisostere
详细信息 查看全文
- 作者：Nils Pemberton ; Henrik Graden ; Emma Evertsson ; Emma Bratt ; Matti Lepist枚 ; Petra Johannesson ; Per H. Svensson
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：July 12, 2012
- 年：2012
- 卷：3
- 期：7
- 页码：574-578
- 全文大小：279K
- 年卷期：v.3,no.7(July 12, 2012)
- ISSN：1948-5875
文摘
An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The cyclic sulfonimidamide ring system could be prepared in two steps from a trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By varying the amino acid, a range of different C-3 substituted sulfonimidamides could be prepared. The compounds could be further derivatized in the aryl ring using standard cross-coupling reactions to yield highly substituted cyclic sulfonimidamides in excellent yields. The physicochemical properties of the final compounds were examined and compared to those of the corresponding carboxylic acid and tetrazole derivatives. The unique nonplanar shape in combination with the relatively strong acidity (pKa 5鈥?) and the ease of modifying the chemical structure to fine-tune the physicochemical properties suggest that this heterocycle can be a valuable addition to the range of available carboxylic acid isosteres.