1449598-85-9

Basic information

• Product Name: 7-fluoro-2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one
• CAS NO: 1449598-85-9
• Molecular Weight: 180.138
• Mol File: 1449598-85-9.mol

Chemical Properties

• CAS DataBase Reference: 7-fluoro-2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one(CAS DataBase Reference)
• NIST Chemistry Reference: 7-fluoro-2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one(1449598-85-9)
• EPA Substance Registry System: 7-fluoro-2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one(1449598-85-9)

Safety Data

• Hazardous Substances Data: 1449598-85-9(Hazardous Substances Data)

Upstream product

• 21717-96-4 2-amino-5-fluoropyridine 
• 108-59-8 malonic acid dimethyl ester 
• 15781-70-1 malonic acid bis-(2,4,6-trichloro-phenyl) ester 

Downstream Products

• 1825352-65-5 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[l,2- b]pyridazin-6-yl)-4H-pyrido[l,2-a]pyrimidin-4-one 

Relevant articles and documents

Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)

SMA is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. We have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional SMN protein. Compound 2 was the first SMN2 splicing modifier tested in clinical trials in healthy volunteers and SMA patients. It was safe and well tolerated and increased SMN protein levels up to 2-fold in patients. Nevertheless, its development was stopped as a precautionary measure because retinal toxicity was observed in cynomolgus monkeys after chronic daily oral dosing (39 weeks) at exposures in excess of those investigated in patients. Herein, we describe the discovery of 1 (risdiplam, RG7916, RO7034067) that focused on thorough pharmacology, DMPK and safety characterization and optimization. This compound is undergoing pivotal clinical trials and is a promising medicine for the treatment of patients in all ages and stages with SMA.

COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY

The present invention provides compounds of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

Characterization and structure-activity relationship study of iminodipyridinopyrimidines as novel hepatitis C virus inhibitor

Upon high-throughput screening of synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified an iminodipyridinopyrimidine (IDPP) scaffold. IDPP did not inhibit HCV replication, but exhibited very potent inhibitory activity on early and late steps of HCV life cycle. Applying an intensive structure-activity relationship (SAR) study, a promising IDPP Lead compound (12c) with excellent potency (EC50 = 10 nM), high safety margin (SI > 2000), and an acceptable stability in human and rat liver microsomes (t1/2 >60 min) was identified. Overall, our results suggest that the IDPP scaffold could be used for the development of novel HCV interventions.

COMPOUNDS FOR TREATING AMYOTROPHIC LATERAL SCLEROSIS

The present invention provides compounds of formula (I) (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof for use in the treatment, prevention and/or delay of progression of amyotrophic lateral sclerosis (ALS). Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

COMPOSITIONS FOR TREATING SPINAL MUSCULAR ATROPHY

The present invention provides pharmaceutical compositions comprising a compound of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the pharmaceutical compositions comprising a compound of formula (I) and their use as medicaments.

Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy

The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure-activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of 160 nM. Daily administration of these compounds to severe SMA Δ7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.

Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine to Treat Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is the leading genetic cause of infant and toddler mortality, and there is currently no approved therapy available. SMA is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. These mutations or deletion

COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY

The present invention provides compounds of formula (I) wherein A, X, Y, R1 and R2 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY

The present invention provides compounds of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY

Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy.