title: Non-peptidic phenyl-based thrombin inhibitors: exploring structural requirements of the S1 specificity pocket with amidines.
abstract: We expand the structural requirements and structure-activity relationship of a novel class of non-peptidic aryl-based thrombin inhibitors through exploration of the S1 specificity pocket of thrombin using flexible and constrained amidines. The most active compound of this class is 11 with Ki = 69 nM, which is ca. 15-fold less potent than constrained guanidine 5.
authors.affiliation: 3-Dimensional Pharmaceuticals, Eagleview Corporate Center, Exton, PA 19341, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lu
authors.forename: B
authors.initials: B
authors.lastname: Tomczuk
authors.forename: R
authors.initials: R
authors.lastname: Bone
authors.forename: L
authors.initials: L
authors.lastname: Murphy
authors.forename: F R
authors.initials: FR
authors.lastname: Salemme
authors.forename: R M
authors.initials: RM
authors.lastname: Soll
mesh_terms: D000578:Amidines / Q000737:chemistry* / Q000494:pharmacology; D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000578:Amidines; D000991:Antithrombins; D006841:Hydrocarbons, Aromatic; D013917:Thrombin