Title:Homologation: A Versatile Molecular Modification Strategy to Drug Discovery
VOLUME: 19 ISSUE: 19
Author(s):Lídia M. Lima*, Marina A. Alves and Daniel N. do Amaral
Affiliation:Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos (INCT-INOFAR;, Laboratorio de Avaliacao e Sintese de Substancias Bioativas, Universidade Federal do Rio de Janeiro, CCS, Cidade Universitaria, Rio de Janeiro- RJ, Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos (INCT-INOFAR;, Laboratorio de Avaliacao e Sintese de Substancias Bioativas, Universidade Federal do Rio de Janeiro, CCS, Cidade Universitaria, Rio de Janeiro- RJ, Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos (INCT-INOFAR;, Laboratorio de Avaliacao e Sintese de Substancias Bioativas, Universidade Federal do Rio de Janeiro, CCS, Cidade Universitaria, Rio de Janeiro- RJ
Keywords:Homologation, Homologous, Molecular modification strategy, Drug discovery, Lead optimization, Organic compounds.
Abstract:Homologation is a concept introduced by Gerhard in 1853 to describe a homologous series in
organic chemistry. Since then, the concept has been adapted and used in medicinal chemistry as one of
the most important strategies for molecular modification. The homologation types, their influence on
physico-chemical properties and molecular conformation are presented and discussed. Its application in
lead-identification and lead optimization steps, as well as its impact on pharmacodynamics/pharmacokinetic
properties and on protein structure is highlighted from selected examples.
• Homologation: definition and types
• Homologous series in nature
• Comparative physico-chemical and conformational properties
• Application in lead-identification and lead-optimization
• Impact on pharmacodynamic property
• Impact on pharmacokinetic property
• Impact on protein structure
• Concluding remarks
• Acknowledgment
• References