Aminotriazines with indole motif as novel, 5-HT7 receptor ligands with atypical binding mode
Authors:
- Damian Kułaga,
- Jolanta Jaśkowska,
- Grzegorz Satała,
- Gniewomir Latacz,
- Paweł Śliwa
Abstract
Developing new and selective 5-HT7R ligands may have a key impact on the treatment of central nervous system diseases including depression. We have found that indoleaminotriazine core fused with alkyl aryl moiety exhibits high affinity and selectivity to 5-HT7R. SAR analysis demonstrated that the ethyl or ethoxy group (5c 5-HT7R Ki = 8 nM; 5d 5-HT7R Ki = 55 nM) is the optimal carbon linker between triazine and aryl moiety. The results of the molecular dynamics simulations show stable interaction with E7.34 upon binding to a 5-HT7R. Compounds 5c and 5d were tested for early ADMET parameters. Compounds are not hepatotoxic and exhibit moderate potential interaction with other drugs metabolized by CYP3A4 or CYP2D6.
- Record ID
- CUT7952a6f4f93d417794f6b019c80fbd11
- Publication categories
- ;
- Author
- Journal series
- Bioorganic Chemistry, ISSN 0045-2068, e-ISSN 1090-2120
- Issue year
- 2020
- Vol
- 104
- Pages
- [1-12]
- Article number
- 104254
- Other elements of collation
- schem.; tab.; wykr.; Bibliografia (na s.) - 12; Bibliografia (liczba pozycji) - 47; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 104
- Keywords in English
- drug design, microwave chemistry, medicinal chemistry, docking, molecular dynamics, 5-HT7R ligands
- DOI
- DOI:10.1016/j.bioorg.2020.104254 Opening in a new tab
- URL
- https://www.sciencedirect.com/science/article/pii/S0045206820315522 Opening in a new tab
- Related project
- Synteza i ocena aktywności nowych ligandów działających na receptory ośrodkowego układu nerwowego (oun). . Project leader at PK: , ,
Projects financed by NCRD [Projekty finansowane przez NCBiR (NCBR (] - Language
- eng (en) English
- License
- Score (nominal)
- 100
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUT7952a6f4f93d417794f6b019c80fbd11/
- URN
urn:pkr-prod:CUT7952a6f4f93d417794f6b019c80fbd11
* presented citation count is obtained through Internet information analysis, and it is close to the number calculated by the Publish or PerishOpening in a new tab system.