Banca de DEFESA: THIAGO MOREIRA PEREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : THIAGO MOREIRA PEREIRA
DATE: 07/06/2024
TIME: 09:00
LOCAL: Auditório da Biblioteca Central
TITLE:

Design and synthesis of trisubstituted 1,2,4-triazoles: structural exploration in the inhibition of GSK-3β for the treatment of Alzheimer’s disease

KEY WORDS:

Alzheimer, 1,24-triazole, GSK-3β, Suzuki-Miyaura, Buchwald-Hartwig, desymmetrization
Ullmann, cyanation, water, degradation.

PAGES: 680
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Currently 55 million people live with dementia worldwide with nearly 10 million new cases every year. Dementia results from a variety of diseases that affect the brain, and its most common form is the Alzheimer’s disease (AD). AD is driven by multiple deleterious factors, among them, the presence of insoluble filaments and protein aggregates. The inhibition of GSK-3β, a kinase involved in many of these deleterious factors, have shown promising results in vivo, emerging as a promising potentially disease-modifying therapeutic class for AD. So, in this work, we designed three series of 1,2,4-triazoles as GSK-3β inhibitors. The synthetic routes to obtain the designed compounds were sucessfully developed. The compounds were tested in vitro against GSK-3β and the results are promissing, with the discover of a hit compound. In addition, the series with best profile was used in the design and synthesis of a new series of GSK-3β degraders (PROTACs).
In parallel to the pharmacological work, we developed the synthesis procedure and molecular diversity exploration of the 1,2,4-triazole nucleus through metal-catalyzed cross-coupling reactions, in addition to a copper-catalyzed cyanation reaction using a non-toxic cyanide source in aqueous medium.

COMMITTEE MEMBERS:
Presidente - 1700480 - ARTHUR EUGEN KUMMERLE
Interna - ***.742.388-** - AUREA ECHEVARRIA AZNAR NEVES LIMA - USP
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Externo à Instituição - JOÃO PAULO DOS SANTOS FERNANDES - UNIFESP
Externo à Instituição - LEANDRO SOTER DE MARIZ E MIRANDA - UFRJ
Externa à Instituição - MARINA AMARAL ALVES - UFRJ
Externo à Instituição - VAGNER DANTAS PINHO