MACROCYCLIZATION OF PEPTIDOMIMETICS

• Main Author: SHIPMAN MICHAEL
• Format: Patent
• Language: Chinese; English
• Published: 25.12.2020
• Subjects: CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES

The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention providesa peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H. 本发明提供了一种通过分离收率和产物分布来进行测量的拟肽大环化的改进方法，所述方法包括用转变诱导性基序取代主链酰胺C＝O键中的一个或多个酰胺C＝O键。所述方法是通用的，其中在一系列环大小(例如，三肽、四肽、五肽和六肽)上均可以见到增强。具体地，本发明提供了一种包括羰基生物电子等排转变诱导性元件的拟肽大环化合物，所述羰基生物电子等排转变诱导性元件具有结构：(I)，其中X是杂原子；并且其中R1到R6各自独立地选自烷基、芳基、杂芳基和H。