Risdiplam Chemical Properties

Density 

1.50±0.1 g/cm3(Predicted)

solubility 

Soluble in DMSO

pka

9.41±0.20(Predicted)

form 

solid

color 

Light yellow to yellow

InChI

InChI=1S/C22H23N7O/c1-14-9-18(26-29-11-15(2)24-21(14)29)17-10-20(30)28-12-16(3-4-19(28)25-17)27-8-7-23-22(13-27)5-6-22/h3-4,9-12,23H,5-8,13H2,1-2H3

InChIKey

ASKZRYGFUPSJPN-UHFFFAOYSA-N

SMILES

C12C=CC(N3CC4(CC4)NCC3)=CN1C(=O)C=C(C1=NN3C=C(C)N=C3C(C)=C1)N=2

Risdiplam Usage And Synthesis

Description

Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier.

Chemical Properties

light yellow powder to yellow powder

Uses

Risdiplam is used in preparation of Imidazopyridazinyl Pyridopyrimidinones for treating spinal muscular atrophy. Gene splicing modulator.

Mechanism of action

Risdiplam works by modifying the splicing process of the SMN2 gene, increasing the production of full-length and functional SMN protein.

Side effects

Body aches or pain, chest pain or tightness, chills, cough, ear congestion, fever, headache, loss of voice, runny or stuffy nose, sneezing, sore throat, trouble breathing, unusual tiredness or weakness and so on.

Synthesis

SNAr reaction between amine 194 and bromopyridine 195 gave 196 in good yield. Reduction by hydrogenation in the presence of a platinum catalyst followed by treatment with di-tert-butyl malonate gave pyridopyrimidone 197 in benzoxazole at elevated temperature in good overall yield for both steps. Mesylation to form sulfonate 198 then participated in a Suzuki coupling with 200 (derived from aryl chloride 199 via Miyaura coupling) to establish the risdiplam core skeleton. N-Boc deprotection of 201 using hydrochloric acid in isopropanol gave risdiplam (XXVI) which was isolated after pH adjustment.

storage

0-4℃ for short term (days to weeks) or -20℃ for long term (months)