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Updated: Jan 5, 2026

Design and Optimization Strategies of a High-Performance Vented Box

Design and Optimization Strategies of a High-Performance Vented Box

Published on: June 9, 2023

Structural simplification: an efficient strategy in lead optimization.

Shengzheng Wang^1,2, Guoqiang Dong¹, Chunquan Sheng¹

¹Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Acta Pharmaceutica Sinica. B

|October 26, 2019

Summary

This summary is machine-generated.

Structural simplification of large molecules improves drug discovery efficiency by enhancing drug-likeness and reducing attrition. This strategy avoids "molecular obesity" and leads to better drug candidates.

Keywords:

11β-HSD, 11β-hydroxysteroid dehydrogenase 3D, three-dimensional ADMET, absorption, distribution, metabolism, excretion and toxicity AM2, adrenomedullin-2 receptor BIOS, biology-oriented synthesis CCK, cholecystokinin receptor CGRP, calcitonin gene-related peptide Drug design Drug discovery GlyT1, glycine transport 1 HBV, hepatitis B virus HDAC, histone deacetylase HLM, human liver microsome JAKs, Janus tyrosine kinases LE, ligand efficiency Lead optimization LeuRS, leucyl-tRNA synthetase MCRs, multicomponent reactions MDR-TB, multidrug-resistant tuberculosis MW, molecular weight NP, natural product NPM, nucleophosmin PD, pharmacodynamic PK, pharmacokinetic PKC, protein kinase C Pharmacophore-based simplification Reducing chiral centers Reducing rings number SAHA, vorinostat SAR, structure‒activity relationship SCONP, structural classification of natural product Structural simplification Structure-based simplification TSA, trichostatin A TbLeuRS, T. brucei LeuRS ThrRS, threonyl-tRNA synthetase VANGL1, van-Gogh-like receptor protein 1 aa-AMP, aminoacyl-AMP aa-AMS, aminoacylsulfa-moyladenosine aaRSs, aminoacyl-tRNA synthetases hA3 AR, human A3 adenosine receptor mTORC1, mammalian target of rapamycin complex 1

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Area of Science:

Medicinal Chemistry
Drug Discovery
Pharmacology

Background:

Designing large hydrophobic molecules for lead optimization often results in poor drug-likeness.
High attrition rates in drug discovery are linked to the development of complex, large molecules.

Purpose of the Study:

To review the application of structural simplification in lead optimization.
To illustrate design strategies and guidelines for structural simplification using case studies.

Main Methods:

Literature review focusing on structural simplification in drug design.
Analysis of case studies, including successful examples leading to marketed drugs.

Main Results:

Structural simplification improves synthetic accessibility and pharmacokinetic profiles.
Truncating unnecessary groups in lead compounds enhances drug-likeness and reduces side effects.

Conclusions:

Structural simplification is a key strategy to improve drug discovery efficiency and success rates.
Avoiding "molecular obesity" through simplification leads to more viable drug candidates and reduces development attrition.