263746-95-8

Usage

Chemical structure

2-[(4-Methylquinazolin-2-yl)amino]quinazolin-4-ol is a derivative of quinazolin-4-ol, with an amino group attached to the 2-position of one of the quinazoline rings, and a methyl group attached to the 4-position of the other ring.

Classification

It belongs to the quinazoline family of chemical compounds.

Pharmaceutical applications

2-[(4-Methylquinazolin-2-yl)amino]quinazolin-4-ol has potential pharmaceutical applications, as quinazoline derivatives have been studied for their pharmacological activities, including anti-inflammatory, antiproliferative, and antihypertensive properties.

Biological activities

The precise biological activities and uses of 2-[(4-Methylquinazolin-2-yl)amino]quinazolin-4-ol have not been fully characterized.

Novelty

It represents a novel scaffold for the development of new drug candidates with potential therapeutic benefits.

Upstream product

• 118-48-9 isatoic anhydride 
• 716-11-0 NSC 403387 

Relevant academic research and scientific papers

COMPOUNDS TARGETING DUAL G-QUADRUPLEX DNA AND STAT3

The present invention relates to novel quinazoline compounds having the formula (I) or (II): (I) (II). The compounds are active both as stabilizers of G-quadruplex DNA structures and as inhibitors of STAT3 phosphorylation. The disclosed compounds are useful in medical treatment, such as the treatment of cancer.

Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization

The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.