Delving into the Latest Updates on 7030B-C5 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PCSK9

Mechanism

PCSK9 inhibitors(Proprotein convertase subtilisin kexin type 9 inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Atherosclerosis

Inactive Indication-

Originator Organization

Institute of Pharmaceutical Biotechnology, Chinese Academy of Medical Sciences

Active Organization

Institute of Pharmaceutical Biotechnology, Chinese Academy of Medical Sciences

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC17H21N5O4

InChIKeyZIVVJVCKDAXYLK-UHFFFAOYSA-N

CAS Registry370871-42-4

Illuminated by insights into the hijacking of host cellular metabolism by coronaviruses, we identified an initial hit compound 7030B-C5, characterized by a xanthine scaffold, via a cellular-level phenotypic screening from a domestic repertoire of lipid-modulating agents. A series of derivatives were synthesized and optimized through comprehensive structure-activity relationship (SAR) studies focusing on the N-1, C-8, and N-7 positions of xanthine and preliminary exploration on the N-3 position and parent nucleus. Compounds 10e, 10f and 10o, featuring modifications at the N-7 position, showed inhibitory activity with half maximal effective concentration (EC₅₀) values in the three-digit nanomolar range against human coronavirus-229E (HCoV-229E). In particular, compound 10o exerted superior potency across various coronavirus strains, including HCoV-229E, HCoV-OC43, and the Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Further investigations revealed that 10o acted on the post-entry stages of virus replication and exhibited a distinctive antiviral mechanism from that of clinically approved nirmatrelvir and molnupiravir. Moreover, drug combination study indicates that 10o operates additively with nirmatrelvir, molnupiravir or omicsynin B4, a dual inhibitor of host proteases for S protein priming. Additionally, in vivo assessments show that 10o has favorable pharmacokinetic and safety profiles compared to its parent compound 7030B-C5. These findings underscore the potential of 10o as a promising antiviral candidate for the treatment of current and potential future coronavirus infections.

100 Deals associated with 7030B-C5

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