Delving into the Latest Updates on KSK-68 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

H3 receptor x σ1 receptor

Mechanism

H3 receptor antagonists(Histamine H3 receptor antagonists), σ1 receptor antagonists(Sigma opioid receptor antagonists)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Uniwersytet Jagiellonski Collegium Medicum

Active Organization

Uniwersytet Jagiellonski Collegium Medicum

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC23H28N2O2

InChIKeyXFNQPNJGEZOKCM-UHFFFAOYSA-N

CAS Registry2566715-91-9

Author: Leniak, Arkadiusz ; Ruiz-Cantero, M Carmen ; Podlewska, Sabina ; Pockes, Steffen ; Szczepańska, Katarzyna ; Humphrys, Laura J ; Calmels, Thierry ; Pilarski, Bogusław ; Bojarski, Andrzej J ; Stark, Holger ; Pietruś, Wojciech ; Łażewska, Dorota ; Kieć-Kononowicz, Katarzyna ; Amata, Emanuele ; Marrazzo, Agostino ; Popiołek-Barczyk, Katarzyna ; Dichiara, Maria ; Leitzbach, Luisa ; Górka, Michał ; Mogilski, Szczepan ; Cobos, Enrique J ; Reiner-Link, David ; Karcz, Tadeusz ; Kalinowska-Tłuścik, Justyna ; Zmysłowski, Adam

In search of new dual-acting histamine H₃/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active in vivo ligands previously studied and described by our team. However, we kept in mind that within the previous series, a pair of closely related compounds, KSK67 and KSK68, differing only in the piperazine/piperidine moiety in the structural core showed a significantly different affinity at sigma-1 receptors (σ₁Rs). Therefore, we first focused on an in-depth analysis of the protonation states of piperazine and piperidine derivatives in the studied compounds. In a series of 16 new ligands, mainly based on the piperidine core, we selected three lead structures (3, 7, and 12) for further biological evaluation. Compound 12 showed a broad spectrum of analgesic activity in both nociceptive and neuropathic pain models based on the novel molecular mechanism.

100 Deals associated with KSK-68

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