Pyridazine Derivatives: Molecular Docking, ADMET Prediction, and Synthesis for Antihypertensive Activity.
Cardiovasc Hematol Agents Med Chem
; 2024 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-39162284
ABSTRACT
INTRODUCTION:
The drug discovery and development domain has witnessed remarkable advancements due to the integration of computational methods, particularly Computer-Aided Drug Design (CADD). Discovering and creating new drugs involves structural modifications to enhance their effectiveness and physical attributes. This frequently includes employing semisynthetic techniques to investigate structure-activity relationships thoroughly. Noticeable progress in molecular biology, computational chemistry, combinatorial chemistry, and highthroughput screening is steering transformative changes in the pharmaceutical industry.BACKGROUND:
High blood pressure or hypertension, a significant health issue, elevates the chances of heart, kidney, and brain complications, among other health concerns. It's a leading cause of untimely mortality globally. Therefore, it is important to search for new antihypertensive compounds that have fewer side effects and higher therapeutic activity.METHODS:
Following molecular docking of the pyridazine derivatives, compounds were subjected to In-silico ADMET analysis. Subsequently, a low molecular weight compound was synthesized. Among the synthesized compounds characterization procedures include TLC, FT-IR, 1HNMR, and LC-MS techniques.RESULT:
Compound 8 exhibited the most favorable molecular docking results with alpha A1 and beta 1 adrenergic receptors. Compounds 3, 5, and 6 fulfilled the essential ADMET criteria. Subsequently, Compounds 3, 4, and 5 underwent additional synthesis and characterization procedures, including TLC, FT-IR, 1H-NMR, and LC-MS techniques.CONCLUSION:
Similar behavior was observed in compounds 6, 8, 10, and 11, all violating Pfizer's 3/75 rules in terms of TPAS. Hydrazinolysis of these b-benzoyl propionic acids produced pyridazine, which was utilized in synthesizing pyridazine derivatives. TLC, FT-IR, 1HNMR, and LCMS have characterized the compounds.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cardiovasc Hematol Agents Med Chem
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
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FARMACOLOGIA
/
HEMATOLOGIA
/
QUIMICA
/
QUIMICA CLINICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
Holanda