title: Novel and potent 17beta-hydroxysteroid dehydrogenase type 1 inhibitors.
abstract: Structure-based drug design using the crystal structure of human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) led to the discovery of novel, selective, and the most potent inhibitors of 17beta-HSD1 reported to date. Compounds 1 and 2 contain a side chain with an m-pyridylmethyl-amide functionality extended from the 16beta position of a steroid scaffold. A mode of binding is proposed for these inhibitors, and 2 is a steroid-based 17beta-HSD1 inhibitor with the potential for further development.
authors.affiliation: Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd., University of Bath, Claverton Down, Bath, BA2 7AY, U.K.
authors.forename: Harshani R
authors.initials: HR
authors.lastname: Lawrence
authors.forename: Nigel
authors.initials: N
authors.lastname: Vicker
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Allan
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mahon
authors.forename: Helena J
authors.initials: HJ
authors.lastname: Tutill
authors.forename: Atul
authors.initials: A
authors.lastname: Purohit
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Reed
authors.forename: Barry V L
authors.initials: BV
authors.lastname: Potter
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; D004970:Estrone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase