1429192-06-2

Upstream product

• 36880-33-8 5-ethyl-thiophene-2-carbaldehyde 
• 4424-17-3 2-aminobenzanilide 
• 2385-27-5 N-phenyl-2-nitrobenzamide 

Downstream Products

• 1429192-44-8 2-(5-ethylthiophen-2-yl)-1-methyl-3-phenyl-2,3-dihydroquinazolin-4(1H)-one 

Relevant academic research and scientific papers

NEW COMPOUNDS HAVING A PROTECTIVE ACTIVITY AGAINST TOXINS WITH INTRACELLULAR ACTIVITY

The present invention concerns a new family of 2,3-dihydroquinazolin-4(1H)-one compounds of general formula (I), and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as ricin or Shiga toxin, for example, using

2,3-DIHYDROQUINAZOLIN-4(1 H)-ONE DERIVATIVES FOR USE IN THE TREATMENT OF VIRAL INFECTIONS

Use of 2,3-dihydroquinazolin-4(lH)-one cyclic derivatives of formula (I) for the treatment of infection with viruses entering cells by endocytosis, especially filovirus such as Ebolavirus.

2,3-dihydroquinazolin-4(1H)-one derivatives for use in the treatment of viral infections

Use of 2,3-dihydroquinazolin-4(1H)-one cyclic derivatives of formula (I) for the treatment of infection with viruses entering cells by endocytosis, especially filovirus such as Ebolavirus

Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses

Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2cycl, an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2cycl and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry.

N -Methyldihydroquinazolinone derivatives of retro-2 with enhanced efficacy against shiga toxin

The Retro-2 molecule protects cells against Shiga toxins by specifically blocking retrograde transport from early endosomes to the trans-Golgi network. A SAR study has been carried out to identify more potent compounds. Cyclization and modifications of Retro-2 led to a compound with roughly 100-fold improvement of the EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay. We also demonstrated that only one enantiomer of the dihydroquinazolinone reported herein is bioactive.