Quinoline Derivatives for Tuberculosis Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for tuberculosis are lengthy, require multiple drugs, and are ineffective against multi-drug resistant strains and latent infections, leading to challenges in patient compliance and the spread of resistant bacterial strains.
Innovation Solution
Development of novel substituted quinoline derivatives with a tertiary nitrogen atom in the alpha position, which inhibit bacterial growth, particularly effective against Mycobacterium tuberculosis and other pathogenic mycobacteria, including latent and drug-resistant strains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current standard treatment regimens are used, then tuberculosis can be treated, but treatment duration is lengthy (6 months or more) and requires multiple drugs
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of quinoline derivatives - specifically introducing a tertiary nitrogen atom in the alpha position of the side chain at the 3-position of the quinoline nucleus. This structural parameter change creates compounds with enhanced bactericidal activity against mycobacteria, enabling shorter treatment durations while maintaining effectiveness
Solution Approach 2:
The patent employs composite materials by combining the quinoline core structure with specific side chain components containing tertiary nitrogen atoms. This composite molecular structure integrates the bactericidal properties of the quinoline nucleus with the enhanced activity conferred by the tertiary nitrogen-containing side chains, resulting in superior anti-tuberculosis agents
2Reliability
If current treatment regimens are used, then tuberculosis can be treated, but patient compliance is difficult due to lengthy treatment and frequent supervision requirements
Solution Approach 1:
The patent modifies molecular parameters by introducing tertiary nitrogen atoms in specific positions of the quinoline derivatives, which enhances the sterilizing activity and bactericidal effect. This allows for reduced treatment duration and potentially less frequent administration, thereby improving patient compliance while maintaining treatment reliability
3Adaptability or versatility
If current treatment regimens are used, then some tuberculosis cases can be treated, but multi-drug resistant strains and latent infections are ineffective
Solution Approach 1:
The patent applies parameter changes by systematically varying the side chain structures attached to the quinoline nucleus, including different tertiary nitrogen-containing groups. These structural modifications create a series of derivatives with enhanced and broadened activity spectra, demonstrating effectiveness against mycobacteria, drug-resistant strains, and latent infections
Solution Approach 2:
The patent achieves universality by designing quinoline derivatives with a core structure that provides broad-spectrum anti-mycobacterial activity. The compounds demonstrate multi-functionality by being effective against various forms of tuberculosis including active disease, latent infections, and multi-drug resistant strains, making them versatile treatment options
4Reliability
If existing antibacterial compounds are used, then some bacterial infections can be treated, but new mechanisms of action are needed for drug-resistant strains
Solution Approach 1:
The patent applies parameter changes by modifying specific positions in the quinoline molecule - particularly the 3-position side chain structure. By introducing tertiary nitrogen atoms at the alpha position and varying the side chain length and substitution patterns, the patent creates compounds with novel mechanisms of action against mycobacteria, achieving effectiveness against drug-resistant strains while maintaining reasonable molecular complexity
Data Source
AI summary
The present invention relates to novel substituted quinoline derivatives according to the general Formula (Ia) or Formula (Ib): the pharmaceutically acceptable acid or base addition salts thereof, the quaternary amines thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof and the N-oxide forms thereof. The claimed compounds are useful for the treatment of a bacterial disease including a mycobacterial disease, particularly those diseases caused by pathogenic mycobacteria such as Mycobacterium tuberculosis, M. bovis, M. avium and M. marinum. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of bacterial diseases and a process for preparing the claimed compounds.