Bicycloheteroaryl-heteroaryl-benzoic acid compounds as retinoic acid receptor beta (RARβ) agonists

Abstract

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as “BHBA compounds”), which, inter alia, are (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARPβ2), to cause or promote neurite development, neurite outgrowth, and / or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.

Description

RELATED APPLICATION[0001]This application is a continuation of U.S. application Ser. No. 15 / 533,492, filed Jun. 6, 2017 entitled “Bicycloheteroaryl-Heteroaryl-Benzoic Acid Compounds as Retinoic Acid Receptor Beta (RARβ) Agonists”. U.S. application Ser. No. 15 / 533,492 is a 35 U.S.C. § 371 national phase application of International application serial no. PCT / EP2015 / 080029 (WO 2016 / 097004), filed on Dec. 16, 2015. International application serial no PCT / EP2015 / 080029 claims priority to United Kingdom patent application number 1422472.9 filed Dec. 17, 2014. The contents of each of the referenced applications are incorporated herein by reference in their entirety.TECHNICAL FIELD[0002]The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds (for convenience, collectively referred to herein as “BHBA compounds”), which, inter alia, are (selective) retinoic acid receptor beta (RARβ) (...

AI Technical Summary

Benefits of technology

The patent text relates to a new invention and its various features and embodiments. The technical effects of the invention are not specified in detail, but it implies that other aspects of the invention may also relate to certain features and embodiments.

Problems solved by technology

As yet, there are no effective treatments for nerve injuries including spinal cord injuries (SCI), stroke, and peripheral nerve injuries.

Second: insufficiency of growth-promoting factors, which are well-known for their ability to promote neurite outgrowth in vitro and to induce some axonal outgrowth when administered to injured cord (see, e.g., Schnell et al., 1994; Lu et al., 2004).

Third: the lack of an appropriate ‘growth programme’ by damaged neurones (see, e.g., Kwon and Tetzlaff, 2001).

The CST forms the major descending pathway in the dorsal columns of the spinal cord and their damage results in functional impairments of some motor tasks.

This results in loss of function of the forelimbs.

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