title: Optimization of halopemide for phospholipase D2 inhibition.
abstract: Halopemide, which was identified by HTS to inhibit phospholipase D2 (PLD2), provided the basis for an exploratory effort to identify potent inhibitors of PLD2 for use as inflammatory mediators. Parallel synthesis and purification were utilized to rapidly identify orally available amide analogs derived from indole 2-carboxylic acids with superior potency versus PLD2.
authors.affiliation: Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139, USA. lauren.monovich@novartis.com
authors.forename: Lauren
authors.initials: L
authors.lastname: Monovich
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mugrage
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Quadros
authors.forename: Karen
authors.initials: K
authors.lastname: Toscano
authors.forename: Ruben
authors.initials: R
authors.lastname: Tommasi
authors.forename: Stacey
authors.initials: S
authors.lastname: LaVoie
authors.forename: Eugene
authors.initials: E
authors.lastname: Liu
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Du
authors.forename: Daniel
authors.initials: D
authors.lastname: LaSala
authors.forename: William
authors.initials: W
authors.lastname: Boyar
authors.forename: Paul
authors.initials: P
authors.lastname: Steed
mesh_terms: D000284:Administration, Oral; D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents; D004294:Domperidone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D010599:Pharmacokinetics; D010739:Phospholipase D / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D004294:Domperidone; C017357:halopemide; D010739:Phospholipase D