Delving into the Latest Updates on LEI-515 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MAGL

Mechanism

MAGL inhibitors(Monoglyceride lipase inhibitors)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

InflammationPain

Inactive Indication-

Originator Organization

Active Organization

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H26Cl2F2N2O3S

InChIKeyWYHRZGBTLDYJGW-PCRMYRMASA-N

CAS Registry2702249-95-2

Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported LEI-515, an aryl sulfoxide, as a peripherally restricted, covalent reversible MAGL inhibitor that reduced neuropathic pain and inflammation in preclinical models. Here, we describe the structure-activity relationship (SAR) of aryl sulfoxides as MAGL inhibitors that led to the identification of LEI-515. Optimization of the potency of high-throughput screening (HTS) hit 1 yielded compound ±43. However, ±43 was not metabolically stable due to its ester moiety. Replacing the ester group with α-CF₂ ketone led to the identification of compound ±73 (LEI-515) as a metabolically stable MAGL inhibitor with subnanomolar potency. LEI-515 is a promising compound to harness the therapeutic potential of MAGL inhibition.

100 Deals associated with LEI-515

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	NL	University of Leiden	05 Dec 2023
Inflammation	Preclinical	US	Indiana University	05 Dec 2023
Pain	Preclinical	US	Indiana University	05 Dec 2023
Pain	Preclinical	NL	University of Leiden	05 Dec 2023