Delving into the Latest Updates on Platencin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

OXSM

Mechanism

OXSM inhibitors(3-Oxoacyl-ACP synthase inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Bacterial Infections

Inactive Indication-

Originator Organization

Merck Research Laboratories Massachusetts LLC

Active Organization

Merck Research Laboratories Massachusetts LLC

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H27NO6

InChIKeyDWUHGPPFFABTIY-RLWZQHMASA-N

CAS Registry869898-86-2

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC₈₀ = 0.0625 μg/mL) against S. aureus compared to platensimycin.

100 Deals associated with Platencin

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