Work

Comprehensive Risdiplam Synthesis Overview: From Cross-Coupling Reliance to Complete Palladium Independence

Year: 2025

Type: article

Abstract: Risdiplam is the first approved small-molecule therapy for spinal muscular atrophy (SMA), a severe, progressive neuromuscular disorder. In addition to its clinical significance, risdiplam is of a great interest for organic and medicinal chemistry due to its complex molecular architecture. Its structure incorporates three highly substituted heterocyclic fragments—imidazo[1,2-b]pyridazine, pyrido[1,2-a]pyrimidin-4-one, and 4,7-diazaspiro[2.5]octane—that serve as both versatile synthetic building blocks and critical pharmacophoric elements for drug design and discovery. The increasing scientific interest in risdiplam has led to numerous publications and patent applications that describe alternative synthetic methodologies. Recently, our group has also developed and introduced efficient, scalable manufacturing routes for the preparation of the target substance and the key intermediates of its synthesis. This mini-review systematically analyzes a plethora of risdiplam assembly strategies and synthetic approaches, covering developments from 2013 to the present.

Source: Molecules

DOI: 10.3390/molecules30224365

Authors: Georgiy Korenev, Maxim B. Nawrozkij, Roman A. Ivanov

Institutions: Sirius University of Science and Technology, Russian Academy of Sciences, Institute of Physiologically Active Compounds

Language: English

Topic: Neurogenetic and Muscular Disorders Research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $3,258

Funder: Russian Science Foundation