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Titolo:
Structure-activity relationships of new NAPAP-analogs
Autore:
Steinmetzer, T; Schweinitz, A; Kunzel, S; Wikstrom, P; Hauptmann, J; Sturzebecher, J;
Indirizzi:
Univ Jena, Inst Biochem & Biophys, D-07743 Jena, Germany Univ Jena Jena Germany D-07743 Biochem & Biophys, D-07743 Jena, Germany Pentapharm Ltd, CH-4002 Basel, Switzerland Pentapharm Ltd Basel Switzerland CH-4002 Ltd, CH-4002 Basel, Switzerland Univ Jena, Ctr Vasc Biol & Med, D-99089 Erfurt, Germany Univ Jena ErfurtGermany D-99089 asc Biol & Med, D-99089 Erfurt, Germany
Titolo Testata:
JOURNAL OF ENZYME INHIBITION
fascicolo: 3, volume: 16, anno: 2001,
pagine: 241 - 249
SICI:
8755-5093(2001)16:3<241:SRONN>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
THROMBIN INHIBITORS; FACTOR-XA; AMINO-ACIDS; DESIGN; 4-AMIDINOPHENYLALANINE; BENZAMIDINE; DERIVATIVES;
Keywords:
thrombin; enzyme inhibitors; anticoagulants; synthesis; elimination; NAPAP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Steinmetzer, T Univ Jena, Inst Biochem & Biophys, Philosophenweg 12, D-07743 Jena, Germany Univ Jena Philosophenweg 12 Jena Germany D-07743 , Germany
Citazione:
T. Steinmetzer et al., "Structure-activity relationships of new NAPAP-analogs", J ENZ INHIB, 16(3), 2001, pp. 241-249

Abstract

Several new analogs of the known thrombin inhibitor NAPAP were synthesized, in which the P2 glycine residue was substituted by natural and unnatural amino acids. The thrombin inhibitory potency was comparable to that of NAPAP. Several of the compounds had inhibition constants lower than 10 nM and avery high selectivity compared to trypsin, factor X-a and plasmin. In addition, analogs were prepared by alkylation of the N-alpha-atom of the 4-amidinophenylalanine in P1 position, which showed a more than 10-fold lower thrombin inhibition. Furthermore, azaglycine was introduced instead of P2 glycine. For most of the inhibitors similar fast elimination rates were seen inrats after intravenous dosing, as found previously for NAPAP. Only some compounds, which contained a second basic group showed a slightly decreased cumulative biliary clearance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 09:42:54