Advanced search ?

Object

Novel functionally selective agonists of the serotonin 5 HT1A receptor

Title: Novel functionally selective agonists of the serotonin 5 HT1A receptor

Author:

Śniecikowska, Joanna

Date:

2018

Type:

Praca doktorska

Abstract:

The subject of the doctoral dissertation was the discovery of a new generation of functionally selective 5-HT1A serotonin receptor agonists, of significant importance in the search for the therapy of psychiatric and neurodegenerative disorders. Designed with the support of molecular modeling, a library of 65 new 1- (1-benzoylpiperidin-4-yl) methanamine derivatives was synthesized by chemical synthesis, of which as many as 48 had subnanomolar affinity, and one of the compounds was characterized by the highest affinity of all the 5 HT1AR ligands described so far (Ki = 0.00016 nM). Seventeen new 5-HT1A receptor agonists with different functional activity profiles were identified, including compounds strongly favoring ERK1 / 2 phosphorylation or β-arrestin recruitment, with very high bias factors (> 1000x). The new series was characterized by high selectivity for the adrenergic α1 and dopaminergic D2 receptors as well as high values of parameters predicting the drug-like and developability properties of the tested compounds (CNS MPO, Fsp3 or LELP).For the lead structure, high selectivity against 44 off-targets, high metabolic stability and favorable ADME parameters have been demonstrated. In rat studies it showed striking and dose-dependent antidepressant activity, observed from very low doses after oral administration (MED = 0.16 mg/kg), achieving an exceptionally high effect size (total reduction of immobility in the Porsolt test).All the obtained compounds are the subject of international patent application WO2017220799.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmacja

Degree grantor:

Jagiellonian University. Medical College. Faculty of Pharmacy. Chair of Pharmaceutical Chemistry. Department of Medicinal Chemistry.

Promoter:

Marcin Kołaczkowski ; Adam Bucki

Date issued:

2018

Identifier:

oai:dl.cm-uj.krakow.pl:4278

Call number:

ZB-128497

ControlNumberVIRTUA:

click here to follow the link

Access rights:

nieograniczony

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Subject and keywords:

functional selectivity biased agonism 5-HT1A receptor agonist serotonin 5-HT1A receptor

Object collections:

Last modified:

May 24, 2021

In our library since:

May 6, 2019

Number of object content hits:

102

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4279

Show description in RDF format:

RDF

Show description in OAI-PMH format:

OAI-PMH

Edition name Date
ZB-128497 May 24, 2021

Objects

Similar

Novel functionally selective agonists of the serotonin 5 HT1A receptor

Śniecikowska, Joanna

2018
Praca doktorska

Characteristics of functional selectivity new 5-HT1A serotonin receptor agonists

Głuch-Lutwin, Monika

2022
Praca doktorska

Structural modifications of arylpiperazine and arylsulfonamide serotonin 5-HT1A and 5-HT7 receptor ligands in search of factors determining selectivity

Bugno, Ryszard

2010
Praca doktorska

Spirohydantion - new ligands of central serotonergic system

Czopek, Anna

2008
Praca doktorska

Antidepressant-like activity in a group of piperazine derivatives

Pytka, Karolina

2013
Praca doktorska

Chemical and pharmacological studies in group of 3,3-disubstituted derivatives of pyrrolidyne-2,5-dion with potential anticonvulsant activity

Chlebek, Iwona

2013
Praca doktorska

Novel anilide and benzylamide derivatives as 5-HT1A/5- HT7 receptor ligands and phosphodiesterase type 4 and 7 inhibitors with potential procognitive and antidepressant activity

Jankowska, Agnieszka Wioleta

2021
Praca doktorska

Novel aryl-alkyl-piperazines with N-acylated amino acids as serotoninergic receptors ligands

Zajdel, Paweł

2006
Praca doktorska
More
×

Citation

Citation style:

Contact details

Address

Medical Library
Medyczna 7
30-688 Krakow

Phone

12 658 72 56
517 385 669

E-Mail

Collecting and Elaboration Department
cyfrowabm@cm-uj.krakow.pl

Visit us!

This page uses 'cookies'. More information