58336-26-8

Usage

Chemical Family

2(1H)-Quinolinone,7-amino-1,4-dimethyl-(9CI) belongs to the quinolinone family.

Amino Derivative

It is an amino derivative of quinolinone, which is a bicyclic aromatic compound.

Molecular Weight

The molecular weight of the compound is 188.23 g/mol.

Physical State

The compound is a yellow solid.

Melting Point

The melting point of the compound is around 105-108°C.

Pharmaceutical Applications

The compound has potential applications in the pharmaceutical industry, particularly in the development of new drugs and pharmaceutical intermediates.

Unique Structure

Its unique structure and properties make it a valuable target for further research and development.

Upstream product

• 19840-99-4 carbostyril 124 
• 74-88-4 methyl iodide 
• 108-45-2 m-phenylenediamine 

Relevant academic research and scientific papers

Synthesis and biological evaluation of quinolone derivatives as transthyretin amyloidogenesis inhibitors and fluorescence sensors

Under certain conditions, numerous soluble proteins possess an inherent tendency to convert into insoluble amyloid aggregates, which are associated with several sporadic and genetic human diseases. Transthyretin (TTR) is one of the more than 30 human amyloidogenic proteins involved in conditions such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Considerable effort has been focused on identifying the native tetrameric TTR stabilizers to inhibit rate-limiting tetramer dissociation and, consequently, ameliorate TTR amyloidogenesis. Here, we describe the design and synthesis of quinolin-2(1H)-one derivatives that could be structurally complementary to the thyroxine-binding site within tetrameric TTR. Among these quinolin-2(1H)-one derivatives, compound 7a allowed 16.7% of V30M-TTR (3.6 μM) fibril formation at the same concentration and 49.6% at a concentration of 1.8 μM. Compound 7a exhibited much greater potency in complex biological samples like human plasma than that observed with tafamidis, the drug approved for the treatment of TTR amyloid cardiomyopathy for wild-type or hereditary TTR-mediated amyloidosis. Furthermore, the unique spectral properties of compound 7a demonstrated its high potential for TTR quantification, imaging sensors, and fluorescent tools to study the mechanism of TTR amyloidogenesis.

Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory

The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously. Although computers have demonstrated the ability to challenge humans in various games of strategy, their use in the automated planning of organic syntheses remains unprecedented. As a result of the impact that such a tool could have on the synthetic community, the past half century has seen numerous attempts to create in silico chemical intelligence. However, there has not been a successful demonstration of a synthetic route designed by machine and then executed in the laboratory. Here, we describe an experiment where the software program Chematica designed syntheses leading to eight commercially valuable and/or medicinally relevant targets; in each case tested, Chematica significantly improved on previous approaches or identified efficient routes to targets for which previous synthetic attempts had failed. These results indicate that now and in the future, chemists can finally benefit from having an “in silico colleague” that constantly learns, never forgets, and will never retire. Multistep synthetic routes to eight structurally diverse and medicinally relevant targets were planned autonomously by the Chematica computer program, which combines expert chemical knowledge with network-search and artificial-intelligence algorithms. All of the proposed syntheses were successfully executed in the laboratory and offer substantial yield improvements and cost savings over previous approaches or provide the first documented route to a given target. These results provide the long-awaited validation of a computer program in practically relevant synthetic design.

Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain

The P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors.

Fluorescent retinoid X receptor ligands for fluorescence polarization assay

Retinoid X receptor (RXR) agonists are candidate agents for the treatment of metabolic syndrome and type 2 diabetes via activation of peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR-heterodimers, which control lipid and glucose metabolism. Reporter gene assays or binding assays with radiolabeled compounds are available for RXR ligand screening, but are unsuitable for high-throughput screening. Therefore, as a first step towards stabilizing a fluorescence polarization (FP) assay system for high-throughput RXR ligand screening, we synthesized fluorescent RXR ligands by modification of the lipophilic domain of RXR ligands with a carbostyril fluorophore, and selected the fluorescent RXR agonist 6-[ethyl(1-isobutyl-2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-7-yl)amino] nicotinic acid 8d for further characterization. Compound 8d showed FP in the presence of RXR and the FP was decreased in the presence of the RXR agonist LGD1069 (2). This compound should be a lead compound for use in high-throughput assay systems for screening RXR ligands.

IMIDAZOPYRIDAZINECARBONITRILES USEFUL AS KINASE INHIBITORS

The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.