Histaminergic and dopaminergic ligands as procognitive agents: synthesis and evaluation of aryloxyalkylpiperazines

• Grant number: 18/04488-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: João Paulo dos Santos Fernandes
• Grantee: Cecília Maria Simões de Queiroz Aranha
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The majority of the neurological disorders are associated to a certain cognitive decline. The mechanisms which role the memory and learning processes are complex and frequently explored in the search for new pharmacotherapeutic targets. Certain pathological conditions, such as Alzheimer's and Parkinson's diseases, vascular dementia and humor disorders affect cognition. Therefore, the search for new molecules that could improve the cognition is continuously developed by pharmaceutical companies as well as in the academic research. It is proposed that these conditions are better treated with a multitarget approach, i.e. by affecting more than one target simultaneously. The roles of the histaminergic and dopaminergic systems are widely known and can be considered among the main targets to get new drugs. In this regard, the project aims to synthesize and evaluate the activity of a set of substituted aryloxyalkylpiperazines with different aromatic cores and also in the terminal nitrogen as histamine H3 and H4 and dopamine D2 and D3 receptors ligands through in vitro binding assays. The compounds will be prepared through methods developed by the group, which usually lead to good yields. It is expected that the designed set bring information about the SAR, important to optimize the activity of new compounds in each target, as well as in the multitarget approach.

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)

CORREA, MICHELLE F.; REINER, DAVID; FERNANDES, GUSTAVO A. B.; VARELA, MARINA T.; ARANHA, CECILIA M. S. Q.; STARK, HOLGER; FERNANDES, JOAO PAULO S.. Profiling of LINS01 compounds at human dopamine D-2 and D-3 receptors. JOURNAL OF CHEMICAL SCIENCES, v. 132, n. 1, DEC 2019. (17/05441-6, 18/03918-2, 18/04488-1, 16/25028-3)

CORREA, M. F.; SILVA, A. B.; PENOMIAN, L.; SIMOES, S. C.; FERNANDES, G. A. B.; ARANHA, C. M. S. Q.; VARELA, M. T.; COSTA-NETO, C. M.; FERNANDES, J. P. S.. EVALUATION AND SAR STUDY OF NOVEL SUBSTITUTED (DIHYDRO)BENZOFURANYL-PIPERAZINES AS HISTAMINE H3R AND H4R LIGANDS. Inflammation Research, v. 68, p. 1-pg., 2019-07-01. (18/04488-1, 18/03918-2, 16/23139-2, 16/25028-3, 17/05441-6)