title: Intramolecular Hydrogen Bond Expectations in Medicinal Chemistry.
abstract: Design strategies centered on intramolecular hydrogen bonds are sometime used in drug discovery, but their general applicability has not been addressed beyond scattered examples or circumstantial evidence. A total of 1053 matched molecular pairs where only one of the two molecules is able to form an intramolecular hydrogen bond via monatomic transformations have been identified across the ChEMBL database. These pairs were used to investigate the effect of intramolecular hydrogen bonds on biological activity. While cases of extreme, conflicting variation of effect emerge, the mean biological activity difference for a pair is close to zero and does not exceed ±0.5 log biological activity for over 50% of the analyzed sample.
authors.affiliation: D.E. Shaw Research , 120W 45th Street, New York, New York 10036, United States.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giordanetto
authors.affiliation: Medicinal Chemistry, Respiratory and Inflammation, Innovative Medicines and Early Development Biotech Unit, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Tyrchan
authors.affiliation: Medicinal Chemistry, Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ulander
keywords: Intramolecular hydrogen bond; conformation; matched molecular pair; molecular design