Bicyclic bis-heteroaryl derivatives as inhibitors of the α-synuclein protein: a patent evaluation of WO2018138088A1. (2nd December 2018)

• Record Type: Journal Article
• Authors: Joubert, Jacques
• Is Part Of: Expert opinion on therapeutic patents. Volume 28:Number 12(2018)
• Page Start: 939
• Page End: 945
• Publication Date: 2018-12-02
• Subjects: Bis-heteroaryl derivatives -- indole -- thiazole -- α-synuclein inhibition -- protein aggregation; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2018.1541234
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: Introduction : Neurodegenerative diseases commonly present misfolding and aggregation of one or more proteins, including α-synuclein, β-amyloid, and tau. Several research efforts have been made to develop therapeutic agents able to reduce the neurotoxic effects of aggregated proteins. Among these, inhibition of α-synuclein by small molecules has been considered as a promising approach. Areas covered : Bis-heteroaryl derivatives based on the N ‐[1‐(1 H ‐indol‐3‐yl)hexan‐2‐yl]‐1, 3‐thiazole‐5‐carboxamide scaffold with different heterocyclic substitutions at the 2-thiazole position showed interesting ability to inhibit self-aggregation of α-synuclein in vitro and were claimed as potential therapeutics for various neurodegenerative diseases. The potential of the presented compounds is evaluated with respect to other similar small molecule modulators of protein aggregation reported in the patent literature. Expert opinion : The compounds presented with ability to inhibit aggregation of α-synuclein in vitro in the low micromolar range. The biggest drawback of the presented application is the absence of pharmacokinetic, toxicity, and in vivo efficacy data. On the other hand, the number of applications in this area by UCB Biopharma SPRL (four published in last 2 years) and promising pharmacokinetic and in vivo data disclosed in a previous patent on similar molecules, indicate that these compounds may hold value as therapeutic agents for neurodegenerative disorders.