title: Monocharged inhibitors of mast cell tryptase derived from potent and selective dibasic inhibitors.
abstract: Truncation of potent and selective dibasic inhibitors afforded monocharged inhibitors of human mast-cell tryptase. Using two classes of analogues as lead structures, several monocharged derivatives were identified with K(i) values ranging from 0.084 to 0.21 microM against the enzyme.
authors.affiliation: Department of Medicinal Chemistry, Axys Pharmaceuticals, Inc. 180 Kimball Way, South San Francisco, CA 94080, USA. dener@chemrx.com
authors.forename: J M
authors.initials: JM
authors.lastname: Dener
authors.forename: V R
authors.initials: VR
authors.lastname: Wang
authors.forename: K D
authors.initials: KD
authors.lastname: Rice
authors.forename: A R
authors.initials: AR
authors.lastname: Gangloff
authors.forename: E Y
authors.initials: EY
authors.lastname: Kuo
authors.forename: W S
authors.initials: WS
authors.lastname: Newcomb
authors.forename: D
authors.initials: D
authors.lastname: Putnam
authors.forename: M
authors.initials: M
authors.lastname: Wong
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D001550:Benzamidines / Q000737:chemistry; D001665:Binding Sites; D001682:Biological Availability; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006146:Guanidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D018716:Molecular Mimicry; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053802:Tryptases; D014508:Urea
chemical_list: C442383:3-(4-guanidinophenyl)-N-(2-phenylethyl)-3-((4-(3,3-diphenylpropylaminocarbonyl)piperazin-1-yl)carbonyl)propanamide; D001550:Benzamidines; D006146:Guanidines; D010879:Piperazines; D015842:Serine Proteinase Inhibitors; D000077489:Piperazine; D014508:Urea; D001120:Arginine; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; C032157:benzamidine