title: The many faces of the adamantyl group in drug design.
abstract: Adamantyl-based compounds are used clinically for the treatment of neurological conditions, as anti-viral agents and as agents against type 2 diabetes. The value of the adamantyl group in drug design is multidimensional. The hydrophobic substituent constant for the adamantyl group has been estimated from the calculated partition coefficients (clogP values) of 31 adamantyl-bearing compounds in the clinic or in development as πadamantyl=3.1, which indicates that the logP value of a compound with high water solubility (logP<<0) could be moved with an adamantyl-based modification to a region that is more clinically useful. The steric bulk of the adamantyl group can: (i) restrict or modulate intramolecular reactivity; and (ii) impede the access of hydrolytic enzymes, thereby increasing drug stability and plasma half life. The value of the adamantyl group in drug design has been recognized most recently in the design of agents to treat iron overload disease (in development), malaria (in clinical trials) and type 2 diabetes (in the clinic).
authors.affiliation: School of Medical Sciences (Pharmacology) and Bosch Institute, University of Sydney, Blackburn Building D06, New South Wales 2006, Australia.
authors.forename: Joe
authors.initials: J
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Obando
authors.forename: Vivian
authors.initials: V
authors.lastname: Liao
authors.forename: Tulip
authors.initials: T
authors.lastname: Lifa
authors.forename: Rachel
authors.initials: R
authors.lastname: Codd
mesh_terms: D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy; D008288:Malaria / Q000188:drug therapy; D012995:Solubility
chemical_list: D000962:Antimalarials; D007004:Hypoglycemic Agents; D007502:Iron Chelating Agents; D000218:Adamantane