title: Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H-imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2.
abstract: We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50) 4-11 nM).
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA. hbreslin@prdus.jnj.com
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Breslin
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Miskowski
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kukla
authors.forename: Hans L
authors.initials: HL
authors.lastname: De Winter
authors.forename: Maria V F
authors.initials: MV
authors.lastname: Somers
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Roevens
authors.forename: Robert W
authors.initials: RW
authors.lastname: Kavash
mesh_terms: D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D007211:Indoles; D011480:Protease Inhibitors; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases