title: Using the Golden Triangle to optimize clearance and oral absorption.
abstract: The Golden Triangle is a visualization tool developed from in vitro permeability, in vitro clearance and computational data designed to aid medicinal chemists in achieving metabolically stable, permeable and potent drug candidates. Classifying compounds as permeable and stable and plotting molecular weight (MW) versus octanol:buffer (pH 7.4) distribution coefficients (logD) or estimated octanol:buffer (pH 7.4) distribution coefficients (elogD) reveals useful trends. Analysis of at least two orthogonal trends, such as permeability and clearance, can be extremely effective in balancing and optimizing multiple properties. In addition, molecular weight and logD impact potency-efficiency calculations, allowing potency, clearance and permeability to be optimized simultaneously.
authors.affiliation: Pfizer Global Research and Development, 10770 Science Center Dr., La Jolla, CA 92121, USA. ted.w.johnson@pfizer.com
authors.forename: Ted W
authors.initials: TW
authors.lastname: Johnson
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Dress
authors.forename: Martin
authors.initials: M
authors.lastname: Edwards
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D018938:Caco-2 Cells; D015195:Drug Design; D006801:Humans; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D008970:Molecular Weight; D009930:Organic Chemicals / Q000378:metabolism; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D009930:Organic Chemicals; D004364:Pharmaceutical Preparations