Delving into the Latest Updates on Chloroxoquinoline with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

An Ti Shu, 安体舒

Target-

Action-

Mechanism-

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Tonghua Maoxiang Pharmaceutical Co. Ltd.

Active Organization

Tonghua Maoxiang Pharmaceutical Co. Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

China (23 Apr 2003),

Neoplasms

Regulation-

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Structure/Sequence

Molecular FormulaC9H6ClNO

InChIKeyXMFXTXKSWIDMER-UHFFFAOYSA-N

CAS Registry23833-97-8

Due to the multifactorial nature of Alzheimer's disease (AD), effective multi-targeted directed ligands (MTDLs) are urgently needed for its treatment as single-target drugs currently encounter therapeutic challenges. Two series of new 4-aminoquinoline derivatives containing an amine or hydroxamic acid terminal were designed, synthesized and evaluated for their cholinesterase inhibition, antioxidant and metal-ion chelation properties. Among them, hydroxamic acid-containing compounds 7r and 7f exhibited the best inhibitor activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), respectively, with the corresponding IC₅₀ values of 0.41 and 1.06 μM, which were superior to those of rivastigmine (IC₅₀ = 5.26, 2.02 μM, respectively). Moreover, compounds 7r and 7f presented excellent ABTS radical scavenging efficiency and selective metal-ion chelation ability such as Cu²⁺ and Fe²⁺. Both molecular docking and enzyme kinetic analysis revealed that compound 7r was a mixed-type inhibitor of AChE. Additionally, the ADME prediction indicated that compounds 7r and 7f have suitable pharmacokinetic and drug-like properties. Furthermore, they demonstrated good safety and blood-brain barrier permeability in cytotoxicity assays and in vivo experiments, respectively. These findings strongly suggest that the 4-aminoquinoline derivatives containing a hydroxamic acid terminal have great potential as promising MTDLs for the treatment of AD, opening new avenues for future therapeutic strategies.

19 Jan 2024·Organic Process Research & Development

Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate

Article

Author: Zitha, Andile ; Klashorst, Gerrit van der ; Malan, Hannes ; Gohain, Mukut ; Malefo, Modibo S. ; Kunyane, Phaladi ; Baruah, Sangeeta ; Scholtz, Chantal

A robust process for the manufacture of the active pharmaceutical ingredient (API) amodiaquine dihydrochloride dihydrate (ADQ, 3), an important antimalarial, is reported. The process consists of a three-step synthetic route that involves a Mannich reaction, substitution with 4,7-dichloroquinoline (4,7-DCQ, 5), and rehydration. Additionally, a cost-competitive process for the production of 4,7-DCQ (5) is also reported wherein 4,7-DCQ (5) was prepared in four steps from meta-chloroaniline (7). 4-Acetamido-2-(diethylaminomethyl)phenol (14), 4,7-DCQ (5), and ADQ (3) were obtained in yields of 92, 89, and 90%, respectively. Costing and process mass intensities of 4,7-DCQ and ADQ are also reported.

01 Jan 2023·Journal of Molecular Structure

New quinoline-thiolactone conjugates as potential antitubercular and antibacterial agents

Author: Faazil, Shaikh ; Kamal, Ahmed ; Asghar, Basim H. ; Basha, Shaikh Thoukhir ; Malik, M. Shaheer ; Shaikh, Iqbal N. ; Obaid, Rami J. ; Ahmed, Saleh A. ; Al-Rooqi, Munirah M. ; Qurban, Jihan ; Jamal, Qazi Mohammad Sajid

Reported the design and synthesis of series of new quinoline-thiolactone I [ n = 8, 9, 10,12; R = MeO, CF₃; R¹ = H, ethoxycarbonyl] and II [ n = 8, 9, 10,12; R = R¹ =H, CF₃; R² = H, Cl] conjugates as potential antitubercular and antibacterial agents.Two of the conjugates, I [ n = 9, 12; R = CF₃; R¹ = H] exhibited good antitubercular activity with MIC value of 8μg/mL.Docking studies showed that the conjugates I [ n = 9, 12; R = CF₃; R¹ = H] exhibited good binding affinity towards the target protein KasA of M. tuberculosis.Two other conjugates also showed decent antibacterial activity with MIC value of 8μg/mL.Further, the docking of conjugate I [ n = 8; R = MeO; R¹ = ethoxycarbonyl] were better than standard drug, linezolid against three different mol. receptors.

100 Deals associated with Chloroxoquinoline

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