Delving into the Latest Updates on Dexecadotril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Retorphan

Target

CD10

Mechanism

enkephalinase inhibitors(Neprilysin inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication-

Inactive Indication

Gastrointestinal Diseases

Originator Organization

Bioprojet Pharma SARL

Active Organization-

Inactive Organization

Bioprojet Pharma SARL

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H23NO4S

InChIKeyODUOJXZPIYUATO-IBGZPJMESA-N

CAS Registry112573-72-5

Anaplastic lymphoma kinase is a tyrosine kinase receptor protein belonging to insulin receptor superfamily. Gene fusions in anaplastic lymphoma kinase are associated with non-small cell lung cancer development. Hence, they are of immense importance in targeted therapies. Thus, for the treatment of non-small cell lung cancer, effective anaplastic lymphoma kinase inhibitors are of great significance. Therefore, our objective is to find hit compounds that could have better inhibitory activity than the existing anaplastic lymphoma kinase inhibitors. Keeping this in mind, in the present study pharmacophore based virtual screening was performed to identify possible anaplastic lymphoma kinase inhibitors. Initially, a five-point common pharmacophore hypothesis was generated based on twelve anaplastic lymphoma kinase inhibitors using PHASE module of Schrödinger. Subsequently, common pharmacophore hypothesis-based screening was conducted against in-trials subset of ZINC database and a total of 1000 hits were identified. The molecules obtained were further screened by three stages of docking using GLIDE software. The docking results reveal that six hit molecules showed higher glide score in comparison with the reference molecules. Finally, pharmacokinetic properties of the hit molecules were also analysed using QikProp programme. The results indicate that molecules namely videx, dexecadotril, chloramphenicol, naficillin were found to have good pharmacokinetic properties and human oral absorption. Moreover, videx, naficillin and chloramphenicol were found to have significant inhibitory activity for mutant (F1174L) anaplastic lymphoma kinase. It was also found that videx exhibited crucial interactions with the Met1199 residue of the native and mutant anaplastic lymphoma kinase protein. Furthermore, PASS algorithm predicted anti-neoplastic activity for all the four molecules. Thus these hits are found to be promising leads for anaplastic lymphoma kinase inhibitors. We believe that this study will be useful for the discovery and designing of more potent anaplastic lymphoma kinase inhibitors in the near future.

01 Jun 2002·Mini-Reviews in Medicinal ChemistryQ3 · MEDICINE

Strategies for Access to Enantiomerically Pure Ecadotril, Dexecadotril and Fasidotril: A Review

Q3 · MEDICINE

Review

Author: Sihel, Miryam ; Plaquevent, Jean-Christophe ; Monteil, Thierry ; Leroux, Richard ; Danvy, Denis

Ecadotril and dexecadotril are powerful and selective inhibitors of neprilysin (NEP, EC 3.4.24.11) and are being developed as therapeutic agents, since they behave as prodrugs of the enantiomers of thiorphan. They exhibit different pharmaceutical profiles (intestinal antisecretatory action for the (R) enantiomer, i.e. dexecadotril, and cardiovascular activity for the (S) enantiomer, i.e. ecadotril). Fasidotril is a related compound which has special interest as an equipotent dual inhibitor of NEP and ACE (EC 3.4.15.1). This behavior confers on fasidotril powerful pharmaceutical properties in the cardiovascular field. This review deals with various synthetic approaches, either published or patented, for access to the enantiomerically pure or highly enriched forms of these drugs. Thus, different methods have been studied, which are taken from different methodologies of resolution procedures and asymmetric synthesis, namely : i- Synthesis from a chiron from the chiral pool ii- Chemical resolution of racemic precursors iii- Enzymatic resolution and desymmetrization of meso starting materials iv- Asymmetric synthesis, including enantioselective catalytic hydrogenation, alkaloid catalyzed asymmetric Michael additions, and diastereoselective alkylation of a chiral derivative. Some of these methods are used in industrial processes leading to the indicated compounds.

01 Jan 1999·Drugs in R & DQ4 · MEDICINE

(S)-Acetorphan, Sinorphan

Q4 · MEDICINE

ArticleOA

Author: &NA;

A review, with 9 references, describing the pharmacodynamic effects of ecadotril, a neutral endopeptidase inhibitor currently undergoing trials for the treatment of hypertension and heart failure.Ecadotril, the (S)-enantiomer of acetorphan, is 2-3-fold more potent than the (R)-enantiomer, retorphan.

100 Deals associated with Dexecadotril

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