title: Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide.
abstract: A novel, 10-step, solid-phase method, based on a secondary amide linker, was developed to construct a diverse library of indole-based SFLLR peptide mimetics as thrombin receptor (protease-activated receptor 1, PAR-1) antagonists. The key steps include stepwise reductive alkylation, urea formation, and Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity.
authors.affiliation: Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA. hzhang@prius.jnj.com
authors.forename: H C
authors.initials: HC
authors.lastname: Zhang
authors.forename: D F
authors.initials: DF
authors.lastname: McComsey
authors.forename: K B
authors.initials: KB
authors.lastname: White
authors.forename: M F
authors.initials: MF
authors.lastname: Addo
authors.forename: P
authors.initials: P
authors.lastname: Andrade-Gordon
authors.forename: C K
authors.initials: CK
authors.lastname: Derian
authors.forename: D
authors.initials: D
authors.lastname: Oksenberg
authors.forename: B E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D000577:Amides / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D018716:Molecular Mimicry; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D005343:Fibrinolytic Agents; D007191:Indazoles; D007211:Indoles; C424723:RWJ 58259; C435605:RWJ-53052; C435606:RWJ-56110; D018179:Receptors, Thrombin; C030374:indole; D014508:Urea