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Enantioselective molecular recognition of chiral molecules that lack specific interaction sites for hydrogen bonding or Lewis acid–base interactions remains challenging. Here we introduce the concept of tailored chiral π‐surfaces toward the maximization of shape complementarity. As we demonstrate for helicenes it is indeed possible by pure van‐der‐Waals interactions (π–π interactions and CH–π interactions) to accomplish enantioselective binding. This is shown for a novel benzo[ghi]perylene trisimide (BPTI) receptor whose π‐scaffold is contorted into a chiral plane by functionalization with 1,1′‐bi‐2‐naphthol (BINOL). Complexation experiments of enantiopure (P)‐BPTI with (P)‐ and (M)‐[6]helicene afforded binding constants of 10 700 M−1 and 550 M−1, respectively, thereby demonstrating the pronounced enantiodifferentiation by the homochiral π‐scaffold of the BPTI host. The enantioselective recognition is even observable by the naked eye due to a specific exciplex‐type emission originating from the interacting homochiral π‐scaffolds of electron‐rich [6]helicene and electron‐poor BPTI. [ABSTRACT FROM AUTHOR]

Sepsis, characterized with high risk of life‐threatening organ dysfunction, represents a major cause of health loss and the World Health Organization (WHO) labelled sepsis as the most urgent unmet medical need in 2017. The emerging biological understanding of the role of RIPK1 in sepsis has opened up an exciting opportunity to explore potent and selective RIPK1 inhibitors as an effective therapeutic strategy for SIRS and sepsis therapy. Herein, we have synthesized a class of highly potent dual‐mode RIPK1 inhibitors occupying both the allosteric and the ATP binding pockets, exemplified by compound 21 (ZB‐R‐55) which is about 10‐fold more potent than GSK2982772, and exhibits excellent kinase selectivity, good oral pharmacokinetics and good therapeutic effects in the LPS‐induced sepsis model, suggesting that compound ZB‐R‐55 is a highly promising preclinical candidate. [ABSTRACT FROM AUTHOR]