Design, synthesis and biological characterization of novel activators of the TrkB neurotrophin receptor
Copyright © 2023 Elsevier Masson SAS. All rights reserved..
Numerous studies have been published about the implication of the neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the pathogenesis of several neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis and motor neuron disease. BDNF activates the TrkB receptor with high potency and specificity, promoting neuronal survival, differentiation and synaptic plasticity. Based on the main structural characteristics of LM22A-4, a previously published small molecule that acts as activator of the TrkB receptor, we have designed and synthesized a small data set of compounds. The lead idea for the design of the new compounds was to modify the third position of the LM22A-4, by introducing different substitutions in order to obtain compounds which will have not only better physicochemical properties but selective activity as well. ADME and toxicity profiles of molecules have been evaluated as well as their biological properties through the TrkB receptor and affinity to promote neurite differentiation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:248 |
|---|---|
| Enthalten in: |
European journal of medicinal chemistry - 248(2023) vom: 15. Feb., Seite 115111 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Antonijevic, Mirjana [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 31.01.2023 Date Revised 02.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejmech.2023.115111 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM351568638 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM351568638 | ||
| 003 | DE-627 | ||
| 005 | 20231226051706.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejmech.2023.115111 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1171.xml |
| 035 | |a (DE-627)NLM351568638 | ||
| 035 | |a (NLM)36645981 | ||
| 035 | |a (PII)S0223-5234(23)00026-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Antonijevic, Mirjana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design, synthesis and biological characterization of novel activators of the TrkB neurotrophin receptor |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.01.2023 | ||
| 500 | |a Date Revised 02.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Numerous studies have been published about the implication of the neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the pathogenesis of several neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis and motor neuron disease. BDNF activates the TrkB receptor with high potency and specificity, promoting neuronal survival, differentiation and synaptic plasticity. Based on the main structural characteristics of LM22A-4, a previously published small molecule that acts as activator of the TrkB receptor, we have designed and synthesized a small data set of compounds. The lead idea for the design of the new compounds was to modify the third position of the LM22A-4, by introducing different substitutions in order to obtain compounds which will have not only better physicochemical properties but selective activity as well. ADME and toxicity profiles of molecules have been evaluated as well as their biological properties through the TrkB receptor and affinity to promote neurite differentiation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Activators | |
| 650 | 4 | |a Neurite differentiation | |
| 650 | 4 | |a Neurotrophins | |
| 650 | 4 | |a Physicochemical properties | |
| 650 | 4 | |a TrkB receptor | |
| 650 | 7 | |a Receptor, trkB |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Brain-Derived Neurotrophic Factor |2 NLM | |
| 650 | 7 | |a N,N',N'-tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide |2 NLM | |
| 650 | 7 | |a Benzamides |2 NLM | |
| 700 | 1 | |a Charou, Despoina |e verfasserin |4 aut | |
| 700 | 1 | |a Ramos, Isbaal |e verfasserin |4 aut | |
| 700 | 1 | |a Valcarcel, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Gravanis, Achille |e verfasserin |4 aut | |
| 700 | 1 | |a Villace, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Callizot, Noelle |e verfasserin |4 aut | |
| 700 | 1 | |a Since, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Dallemagne, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Charalampopoulos, Ioannis |e verfasserin |4 aut | |
| 700 | 1 | |a Rochais, Christophe |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of medicinal chemistry |d 1994 |g 248(2023) vom: 15. Feb., Seite 115111 |w (DE-627)NLM106608835 |x 1768-3254 |7 nnns |
| 773 | 1 | 8 | |g volume:248 |g year:2023 |g day:15 |g month:02 |g pages:115111 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejmech.2023.115111 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 248 |j 2023 |b 15 |c 02 |h 115111 | ||