Novel nitrogen containing fused scaffolds for medicinal and material chemistry

• Grant number: 24/08603-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2025
• End date: December 31, 2027
• Field of knowledge: Health Sciences - Pharmacy
• Agreement: Research Foundation - Flanders (FWO)
• Principal Investigator: Flavio da Silva Emery
• Grantee: Flavio da Silva Emery
• Principal researcher abroad: Wim Dehaen
• Institution abroad: University of Leuven, Leuven (KU Leuven) , Belgium
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto

Abstract

Nitrogen-containing heteroaromatic rings are crucial fragments that can be investigated in fragment based drug design (FBDD) efforts as potential ligands. This has been shown before in the development of lead fragment molecules to approved, marked drugs such as vemurafenib. In thisproject, the applicants in Brazil (Ribeirao Preto campus of University of Sao Paulo) and Flanders (KULeuven) will work together to use isocyanide building blocks for the synthesis of three novel classes of nitrogen-containing scaffolds. This project is in part based on preliminary results generated after a research exchange from a Brazilian Ph D student to KU Leuven (current). These different scaffolds will then be used in FBDD in the Center for the Research and Advancement of Fragments and Molecular Targets, coordinated by the Brazilian PI, which integrates AI with FBDD to discover novel anti-infective agents, particularly targeting neglected diseases. The postfunctionalized derivatives willbe screened for biological activities (anticancer, antiviral, kinase inhibition) in collaboration with the Rega institute (KU Leuven). Some of the new polyfused heterocycles will be highly fluorescent, and the photophysical properties of these compounds will be measured. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GODOI, BRUNA F.; BUENO, JESSICA D.; SILVA, WEMENES J. L.; DA PURIFICACAO, ALINE D.; LEITE, PEDRO I. P.; DOS SANTOS, THIAGO; FREITAS, MURILLO; SILVA, DANIEL G.; SILVA, TAIS C.; DE MORAES, JOSUE; et al. Quinazolinones as Bioisosteres of Naphthoquinones: A Path to Potent HsDHODH Inhibitors with Optimized Properties. ACS Medicinal Chemistry Letters, v. N/A, p. 10-pg., 2025-09-16. (21/10084-3, 23/07081-8, 23/08418-6, 22/03521-0, 13/08216-2, 20/05369-6, 23/11804-5, 21/13237-5, 24/08603-0, 20/06190-0)