491833-28-4

Usage

Uses

Used in Pharmaceutical Industry:
1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)is used as a potential drug candidate for its potential biological activity. 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-'s unique structure and chirality may contribute to its efficacy in treating various medical conditions, although further research is required to determine its specific applications and pharmacological properties.
Used in Medicinal Chemistry:
1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)is used as a building block for the synthesis of other bioactive compounds in medicinal chemistry. Its structural features and chirality may enable the development of novel therapeutic agents with improved efficacy and selectivity. Further exploration of its chemical properties and reactivity is necessary to fully harness its potential in the synthesis of new pharmaceuticals.

Upstream product

• 491833-25-1 (1R,3S,5S,8aS)-1,3-bis(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-phenyltetrahydro-3H,8H-oxazolo[4,3-c][1 ,4]oxazin-8-one 
• 620-72-4 phenyl 2-bromoacetate 
• 125244-73-7 2-nitro-1-(1-pyrrolidinyl)ethanone 
• 491833-25-1 C₂₈H₂₅NO₇ 
• 4442-54-0 2,3-dihydro-1,4-benzodioxin-6-carboxylic acid 
• 74053-94-4 ethyl 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanoate 

Downstream Products

• 245329-78-6 D-threo-1-(3',4'-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol 
• 956895-37-7 N-[2-hydroxy-2-(2,3-dihydrobenzo[β][1,4]dioxin-6-yl)-1-pyrrolidin-1-ylmethyl-ethyl]-3-(4-methoxy-phenoxy)-propionamide 
• 1092473-70-5 C₂₆H₃₂N₂O₃ 
• 491833-29-5 (1R,2R)-octanoic acid [2-(2',3'-dihydro-benzo[1,4]dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide 

Relevant academic research and scientific papers

Concise and efficient synthesis of eliglustat

Eliglustat, a ceramide glucosyltransferase inhibitor, was synthesized in six steps with 28.4% overall yield. The key features include the use of a diastereoselective aldol reaction to construct two contiguous stereocenters and a selective sulfonylation of a 1,3-diol catalyzed by dibutyltin oxide.

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storag

Development of an Efficient and Scalable Asymmetric Synthesis of Eliglustat via Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation

An efficient and scalable synthesis of eliglustat (1) is herein reported. This novel route features a three-step telescoped process to afford the α-dibenzylamino β-ketoester 6 in 85% overall yield from commercially available 1,4-benzodioxane-6-carboxylic acid 7. The key intermediate 5 was obtained via an efficient ruthenium-catalyzed DKR-ATH reaction, which afforded the desired product in 90% isolated yield with >99:1 dr and 99.7% ee on a 100 g scale. In addition, the amidation of sterically hindered carboxylic acid 14 was optimized and amenable to scale-up. This process not only gives a desirable total yield but also avoids hazardous conditions and chromatographic purification. The robustness of this synthesis was successfully performed on a multigram scale to afford 1 with >99.9% de and >99.9% ee in 56.8% overall yield in nine steps.

AN IMPROVED PROCESS FOR THE PREPARATION OF ELIGLUSTAT AND ITS INTERMEDIATE

The present invention relates to an improved process for the preparation of N-((1R,2R)-1-(2,3- dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)octanamide (A), which is known as ELIGLUSTAT and its pharmaceutically acceptable salts, comprising the formation of novel intermediate metal complex (III), which on hydrolysis in presence of acid provides amine compound (IV) (as described herein), which is treated with pyrrolidine and subsequently reduced to convert into Eliglustat (A).

Eliglustat intermediate and preparation method thereof

The invention relates to an eliglustat intermediate and a preparation method thereof, and provides a series of intermediate compounds for preparing eliglustat, and a preparation method of the intermediates. With the method provided by the invention, raw materials and a transition metal catalyst are subjected to an asymmetric hydrogenation reaction on under certain conditions, and then a series ofreactions are performed to prepare eliglustat. The method provided by the invention is simple and controllable in reaction conditions and easy for industrial production.

Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3

There remain no approved therapies for rare but devastating neuronopathic glyocosphingolipid storage diseases, such as Sandhoff, Tay-Sachs, and Gaucher disease type 3. We previously reported initial optimization of the scaffold of eliglustat, an approved therapy for the peripheral symptoms of Gaucher disease type 1, to afford 2, which effected modest reductions in brain glucosylceramide (GlcCer) in normal mice at 60 mg/kg. The relatively poor pharmacokinetic properties and high Pgp-mediated efflux of 2 prompted further optimization of the scaffold. With a general objective of reducing topological polar surface area, and guided by multiple metabolite identification studies, we were successful at identifying 17 (CCG-222628), which achieves remarkably greater brain exposure in mice than 2. After demonstrating an over 60-fold improvement in potency over 2 at reducing brain GlcCer in normal mice, we compared 17 with Sanofi clinical candidate venglustat (Genz-682452) in the CBE mouse model of Gaucher disease type 3. At doses of 10 mg/kg, 17 and venglustat effected comparable reductions in both brain GlcCer and glucosylsphingosine. Importantly, 17 achieved these equivalent pharmacodynamic effects at significantly lower brain exposure than venglustat.

Preparation method of gaucher disease treatment drug eliglustat

The invention relates to a preparation method of a gaucher disease treatment drug eliglustat. The preparation method comprises the following steps: using S-isopropyl-2-oxazolidinone as a raw material,carrying out a condensation reaction, a bromination reaction, a substitution reaction, a hydrolysis reaction, a condensation reaction and a reduction reaction to obtain eliglustat, and carrying out salt forming and two-step purification on the eliglustat to obtain high-purity eliglustat tartrate. According to the method, the chiral center is completely synthesized from the starting material, so that the reaction steps are reduced, the production period is shortened, the synthesis efficiency of the chiral center is improved, the yield of the final product is improved, the salt forming steps are optimized in detail, and the qualified quality control of the bulk drug is ensured.

STABLE N-((1R,2R)-1-(2,3-DIHYDROBENZO[B][1,4]DIOXIN-6-YL)-1-HYDROXY-3-(PYRROLIDIN-1-YL)PROPAN-2-YL) OCTANAMIDE (2R,3R)-2,3-DIHYDROXYSUCCINATE PREMIX AND PROCESS FOR PREPARATION THEREOF

The present invention related to stable N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)- 1-hydroxy-3- (pyrrolidin-1-yl)propan-2-yl) octanamide (2R,3R)- 2,3-dihydroxysuccinate premix of formula (Ia) and its process for preparation thereof. The present invention also related to process for the preparation of N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6- yl)-1-hydroxy-3- (pyrrolidin-1-yl) propan-2-yl) octanamide of formula (I) and pharmaceutically acceptable salts.

Method for preparing Eliglustat

The invention discloses a method for preparing Eliglustat. The Eliglustat is an effective specific glucosylceramide systhase inhibitor, which can be used for treating type-I Gaucher disease. The invention provides the synthetic method of Eliglustat, which comprises the following steps: 1,4-benzdioxan-6-formaldehyde and a chiral ligand are subjected to an adiastereoselectivity Aldol reaction, and then subjected to a reduction reaction, replacement and a Staudinger reaction, and an amidation reaction to obtain Eliglustat. The method has the advantages of easy acquisition of raw material, simpleoperation, high product yield and purity, and easy industrial large production.

Synthesis of UDP-glucose: N-acylsphingosine glucosyl transferase inhibitors

Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.