Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a ceteris paribus approach.
Expert Opin Drug Discov
; 19(8): 991-1009, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38898679
ABSTRACT
BACKGROUND:
Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors. RESEARCH DESIGN ANDMETHODS:
A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed.RESULTS:
The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors.CONCLUSIONS:
The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Trombina
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Antitrombinas
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Compuestos Heterocíclicos
/
Nitrógeno
Límite:
Humans
Idioma:
En
Revista:
Expert Opin Drug Discov
Año:
2024
Tipo del documento:
Article
País de afiliación:
India