Therapeutic applications of serine protease inhibitors

Bibliography

• SMITH HJ, SIMONS C: Protease and Peptidase Inhibition - Recent Potential Targets for Drug Development. Taylor & Francis, London and New York (2002):1–412 (and references cited therein).
   Google Scholar
• ••Excellent and exhaustive textbook on thedesign of protease inhibitors with different therapeutic applications.
   Google Scholar
• BABINE RE, BENDER SL: Molecular recognition of protein-ligand complexes: applications to drug design. Chem. Rev (1997) 97:1359–1472.
   PubMed Web of Science ®Google Scholar
• SUPURAN CT, SCOZZAFAVA A, MASTROLORENZO A: Bacterial proteases: current therapeutic use and future prospects for the development of new antibiotics. Expert Opin. Ther. Patents(2001) 11:221–259.
   Web of Science ®Google Scholar
• SUPURAN CT, SCOZZAFAVA A, CLARE BW: Bacterial protease inhibitors. Med. Res. Rev (2002) 22:1–44.
   PubMedGoogle Scholar
• HAUPTMANN J, STURZEBECHER J: Synthetic inhibitors of thrombin and Factor Xa: from bench to bedside. Thrombosis Res. (1999) 93:203–241.
   PubMed Web of Science ®Google Scholar
• SANDERSON PE: Small, noncovalent serine protease inhibitors. Med. Res. Rev (1999) 19:179–197.
   PubMed Web of Science ®Google Scholar
• WILEY MR, FISHER MJ: Small-molecule direct thrombin inhibitors. Expert Opin. Ther. Patents (1997) 7:1265–1282.
   Web of Science ®Google Scholar
• BETZ A: Recent advances in Factor Xa inhibitors. Expert Opin. The]: Patents (2001) 11:1007–1017.
   Web of Science ®Google Scholar
• COBURN CA: Small-molecule direct thrombin inhibitors: 1997-2000. Expert Opin. Ther. Patents (2001) 11:721–738.
   Web of Science ®Google Scholar
• STEINMETZER T, HAUPTMANN J, STURZEBECHER J: Advances in the development of thrombin inhibitors. Expert Opin. Investig. Drugs (2001) 10:845–864.
   PubMed Web of Science ®Google Scholar
• WHITTAKER M, FLOYD CD, BROWN P, GEARING AJ: Design and therapeutic application of matrix metalloproteinase inhibitors. Chem. Rev (1999) 99:2735–2776.
   PubMed Web of Science ®Google Scholar
• SUPURAN CT, SCOZZAFAVA A: Matrix metalloproteinase inhibitors. In: Protease and Peptidase Inhibition: Recent Potential Targets for Drug Development. Smith HJ, Simons C (Eds), Taylor & Francis, London (2001)35–52.
   Google Scholar
• BARRETT AJ, RAWLINGS ND, WOESSNER JF: Handbook of Proteolytic Enzymes (CD-ROM) Academic Press, London (1998).
   Google Scholar
• OTTO HH, SCHIRMEISTER T: Cysteine proteases and their inhibitors. Chem. Rev (1997) 97:133–172.
   PubMed Web of Science ®Google Scholar
• KATONA G, WILMOUTH RC, WRIGHT PA et al.: X-ray structure of a serine protease acyl-enzyme complex at O.95A resolution. J. Biol. Chem. (2002) 14:14 (In Press).
   Google Scholar
• WILMOUTH RC, EDMAN K, NEUTZE R et al.: X-ray snapshots of serine protease catalysis reveal a tetrahedral intermediate. Nat. Struct. Biol. (2001) 8:689–694.
   PubMedGoogle Scholar
• ASH EL, SUDMEIER JL, DAY RM et al.: Unusual 1H NMR chemical shifts support (His) Cepsilon 1...0C H-bond: proposal for reaction-driven ring flip mechanism in serine protease catalysis. Proc. Natl Acad. ScL USA (2000) 97:10371–10376.
   Google Scholar
• SCHECHTER I, BERGER A: On the sizeof the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. (1967) 27:157–162.
   PubMed Web of Science ®Google Scholar
• BODE W, HUBER R: Natural protein protease inhibitors and their interaction with proteases. Eur. .1 Biochem. (1992) 204:433–451.
   PubMedGoogle Scholar
• FRIGERIO F, CODA A, PUGLIESE L et al: Crystal and molecular structure of the bovine alpha-chymotrypsin-eglin c complex at 2.0 A resolution.Biol. (1992)225:107–123.
   PubMedGoogle Scholar
• UMEZAWA H, AOYAGI T, MORISHIMA H, KUNIMOTO S, MATSUZAKI M: Chymostatin, a new chymotrypsin inhibitor produced by actinomycetes. Antibiot. (Tokyo) (1970) 23:425–427.
   PubMedGoogle Scholar
• AOYAGI T, MIYATA S, NANBO M, KOJIMA F, MATSUZAKI M: Biological activities of leupeptins. I Antibiot. (Tokyo) (1969) 22:558–568.
   PubMed Web of Science ®Google Scholar
• UMEZAWA H: Protease inhibitors produced by microorganisms. Acta. Biol. Med. Gel: (1977) 36:1899–1915.
   PubMedGoogle Scholar
• LEE AY, SMITKA TA, BONJOUKLIAN R, CLARDY J: Atomic structure of the trypsin-A90720A complex: a unified approach to structure and function. Chem. Biol. (1994) 1:113–117.
   PubMedGoogle Scholar
• MARYANOFF BE, QIU X, PADMANABHAN KP et al: Molecular basis for the inhibition of human alpha-thrombin by the macrocyclic peptide cyclotheonamide A. Proc. Nati Acad. Sci. USA (1993) 90:8048–8052.
   PubMed Web of Science ®Google Scholar
• NIENABER VL, AMPARO EC: A noncleavable retro-binding peptide that spans the substrate binding cleft of serine proteases. Atomic structure of nazumamide A: human thrombin.j Am. Chem. Soc. (1996) 118:6807–6810.
   Google Scholar
• LEVI M: Hemostasis in the 21st century. Neth. J. Med. (1999) 55:280–286.
   PubMedGoogle Scholar
• GRESELE P, AGNELLI G: Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. (2002) 23:25–32.
   PubMed Web of Science ®Google Scholar
• MURRAY CJ, LOPEZ AD: Mortality bycause for eight regions of the world: Global Burden of Disease Study. Lancet (1997) 349:1269–1276.
   PubMed Web of Science ®Google Scholar
• SCHMAIER AH: Plasma kallikrein/Idnin system: a revised hypothesis for its activation and its physiologic contributions. Carr. Opin. Hematol (2000) 7:261–265.
   PubMed Web of Science ®Google Scholar
• DAHLBACK B: Blood coagulation. Lancet (2000) 355:1627–1632.
   PubMed Web of Science ®Google Scholar
• EIGENBROT C, KIRCHHOFER D: New insight into how tissue factor allosterically regulates Factor VIIa. Trends Cardiovasc. Med. (2002) 12:19–26.
   PubMedGoogle Scholar
• BUTENAS S, BRUMMEL KE, BRANDA RF, PARADIS SG, MANN KG: Mechanism of Factor VIIa-dependent coagulation in hemophilia blood. Blood (2002) 99:923–930.
   PubMedGoogle Scholar
• CASTELLINO FJ: Gene targeting in hemostasis: protein C. Front Biosci. (2001) 6:807–819.
   Google Scholar
• OKAJIMA K: Regulation of inflammatory responses by natural anticoagulants. Inman°log. Rev (2001) 184:258–274.
   Google Scholar
• LUNEN HR: Elements of the fibrinolytic system. Fibrinogen (2001) 936:226–236.
   Google Scholar
• BEDNAR MM: Stroke: antithrombin versus antiplatelet therapy. Expert Opin. Investig. Drugs (2000) 9:355–369.
   PubMedGoogle Scholar
• VACCA JP: New advances in the discovery of thrombin and Factor Xa inhibitors. Curt: Opin. Chem. Biol. (2000) 4:394–400.
   PubMed Web of Science ®Google Scholar
• ••Excellent review on the development ofthrombin and fXa inhibitors.
   Google Scholar
• HIRSH J: Modulating the coagulation cascade: new targets for antithrombotics and anticoagulants. Am. Heart J. (2001) 142:S3–S8.
   Google Scholar
• GOLDSACK NR, CHAMBERS RC, DABBAGH K, LAURENT GJ: Thrombin. Int.j Biochem. Cell Biol. (1998) 30:641–646.
   PubMed Web of Science ®Google Scholar
• SIESS W: Platelet receptors: the thrombinreceptor. Handb. Exp. Pharmacol (1997) 126:101–116.
   Google Scholar
• KAHN ML, ZHENG Y-W HUANG W et al: A dual thrombin receptor system for platelet activation. Nature (1998) 394:690–694.
   PubMed Web of Science ®Google Scholar
• WHISSTOCK JC, PIKE RN, JIN L et al.:Conformational changes in serpins: II. The mechanism of activation of antithrombin by heparin. J. Ma Biol. (2000) 301:1287–1305.
   Google Scholar
• BODE W, TURK D, KARSHIKOV A: The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human a-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry and structure-function relationships. Protein ScL (1992) 1:426–471.
   Google Scholar
• STUBBS MT, OSCHKINAT H, MAYR I et al: The interaction of thrombin with fibrinogen. A structural basis for its specificity. f.ir.j Biochem. (1992) 206:187–195.
   Google Scholar
• DI CERA E: Site-specific thermodynamics:Understanding cooperativity in molecular recognition. Chem. Rev (1998) 98:1563–1591.
   PubMed Web of Science ®Google Scholar
• SIXMA JJ, DE GROOT PG: The ideal antithrombotic drug. Thromb. Res. (1992) 68:507–512.
   PubMedGoogle Scholar
• MARTIN PD, ROBERTSON W, TURK D, HUBER R, BODE W, EDWARDS BF: The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution. J. Biol. Chem. (1992) 267:7911–7920.
   PubMedGoogle Scholar
• ROSE T, DI CERA E: Three-dimensional modeling of thrombin-fibrinogen interaction. Biol. Chem. (2002) 277:18875–18880.
   Google Scholar
• BAJUSZ S, SZELL E, BAGDY D et al: Highly active and selective anticoagulants: D-Phe-Pro-Arg-H, a free tripeptide aldehyde prone to spontaneous inactivation and its stable N- methyl derivative, D-MePhe-Pro-Arg-H. I Med. Chem. (1990) 33:1729–1735.
   PubMed Web of Science ®Google Scholar
• BACHAND B, TARAZI M, ST-DENTS Y et al.: Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:287–290.
   Google Scholar
• KETTNER C, MERSINGER L, KNABB R: The selective inhibition of thrombin by peptides of boroarginine.j Biol. Chem. (1990) 265:18289–18297.
   PubMed Web of Science ®Google Scholar
• TAPPARELLI C, METTERNICH R, EHRHARDT C et al.: In vitro and M vivo characterization of a neutral boron-containing thrombin inhibitor. J. Biol. Chem. (1993) 268:4734–4741.
   PubMed Web of Science ®Google Scholar
• WEBER PC, LEE SL, LEWANDOWSKI FA, SCHADT MC, CHANG CW, KETTNER CA: Kinetic and crystallographic studies of thrombin with Ac-(D)Phe-Pro-boroArg-OH and its lysine, amidine, homolysine and ornithine analogs. Biochemistry (1995) 34:3750–3757.
   PubMedGoogle Scholar
• VON MATT A, EHRHARDT C, BURKHARD P, METTERNICH R, WALKINSHAW M, TAPPARELLI C: Selective boron-containing thrombin inhibitors-X-ray analysis reveals surprising binding mode. Bioorg. Med. Chem. (2000) 8:2291–2303.
   PubMedGoogle Scholar
• BASU S, LARSSON A, MATTSSON C et al.: Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock. Expert Opin. Investig. Drugs (2000) 9:1129–1137.
   PubMed Web of Science ®Google Scholar
• DAHLGREN A, JOHANSSON PO, KVARNSTROM I, MUSIL D, NILSSON I, SAMUELSSON B: Novel Mmorpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors: design, synthesis and X-ray crystal Structure of an enzyme inhibitor complex. Bioorg. Med. Chem. (2002) 10:1829–1839.
   PubMedGoogle Scholar
• DAHLGREN A, BRANALT J, KVARNSTROM I, NILSSON I, MUSIL D, SAMUELSSON B: Synthesis of potential thrombin inhibitors. Incorporation of tartaric acid templates as P2 proline mimetics. Bioorg. Med. Chem. (2002) 10:1567–1580.
   PubMedGoogle Scholar
• PETERLIN-MASIC L, KIKELJ D: Arginine mimetics. Tetrahedron (2001) 57:7073–7105.
   Web of Science ®Google Scholar
• PETERLIN-MASIC L, JURCA A, MARINKO P, JANCAR A, KIKELJ D: A general synthetic approach to novel conformationally restricted arginine side chain mimetics. Tetrahedron (2002) 58:1557–1563.
   Google Scholar
• CLARE BW, SCOZZAFAVA A, BRIGANTI F, IORGA B, SUPURAN CT: Protease inhibitors. Part 2. Weakly basic thrombin inhibitors incorporating sulfonyl-aminoguanidine moieties as 51 anchoring groups: synthesis and structure-activity correlations. Enzyme Inhib. (2000) 15:235–264.
   Google Scholar
• SCOZZAFAVA A, BRIGANTI F, SUPURAN CT: Protease inhibitors. Part 3. Synthesis of nonbasic thrombin inhibitors incorporating pyridinium-sulfanilylguanidine moieties at the P1 site. Ear. J. Med. Chem. (1999) 34:939–952.
   Google Scholar
• SUPURAN CT, BRIGANTI F, SCOZZAFAVA A, ILIES MA: Protease inhibitors: Part 4. Synthesis of weakly basic thrombin inhibitors incorporating pyridinium-sulfanilylaminoguanidine moieties. I Enzyme Inhib. (2000) 15:335–356.
   Google Scholar
• SUPURAN CT, SCOZZAFAVA A, BRIGANTI F, CLARE BW: Protease inhibitors: synthesis and QSAR study of novel classes of nonbasic thrombin inhibitors incorporating sulfonylguanidine and O-methylsulfonylisourea moieties at Pl. Med. Chem. (2000) 43:1793–1806.
   Web of Science ®Google Scholar
• •A new type of Si anchoring moiety leading to weakly basic SPIs.
   Google Scholar
• CLARE BW, SCOZZAFAVA A, SUPURAN CT: Protease inhibitors, part 13: Specific, weakly basic thrombin inhibitors incorporating sulfonyl dicyandiamide moieties in their structure.' Enzyme Inhib. (2001) 16:1–13.
   PubMedGoogle Scholar
• SUPURAN CT, MANOLE G, DINCULESCU A et al.: Carbonic-anhydrase inhibitors. .5. Pyrylium-salts in the synthesis of isozyme-specific inhibitors. Pharm. Sci. (1992) 81:716–719.
   Google Scholar
• SUPURAN CT, ILIES MA, SCOZZAFAVA A: Carbonic anhydrase inhibitors - Part 29:interaction of isozymes I, II and IV with benzolamide-like derivatives. Ear: J. Med. Chem. (1998) 33:739–751.
   Google Scholar
• SUPURAN CT, SCOZZAFAVA A, ILIES MA et al.: Carbonic anhydrase inhibitors - Part 53 - Synthesis of substituted-pyridinium derivatives of aromatic sulfonamides: the first nonpolymeric membrane-impermeable inhibitors with selectivity for isozyme IV. Ear: Med. Chem. (1998) 33:577–594.
   Google Scholar
• SCOZZAFAVA A, BRIGANT1F, ILIES MA, SUPURAN CT: Carbonic anhydrase inhibitors: synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. Med. Chem. (2000) 43:292–300.
   Web of Science ®Google Scholar
• SUPURAN CT, SCOZZAFAVA A, ILIES MA, BRIGANTI F: Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating 2,4,6-trisubstituted-pyridinium-ethylcarboxamido moieties possessing membrane-impermeability and in vivo selectivity for the membrane-bound (CA IV) versus the cytosolic (CA I and CA II) isozymes. .1 Enzyme Inhib. (2000) 15:381–401.
   PubMed Web of Science ®Google Scholar
• STEINMETZER T, KONISHI Y: Tripeptidyl pyridinium methyl ketones as potent active site inhibitors of thrombin. Bioorg. Med. Chem. Lett. (1996) 6:1677–1682.
   Google Scholar
• RIPKA AS, RICH DH: Peptidomimetic design. Carr. Opin. Chem. Biol. (1998) 2:441–452.
   PubMed Web of Science ®Google Scholar
• BROWN FJ, ANDISIK DW, BERNSTEIN PR et al.: Design of orally-active, nonpeptidic inhibitors of human leukocyte elastase. Med. Chem. (1994) 37:1259–1261.
   Google Scholar
• HO JZ, GIBSON TS, SEMPLE JE: Novel,potent noncovalent thrombin inhibitors incorporating p(3)- lactam scaffolds. Bioorg. Med. Chem. Lett. (2002) 12:743–748.
   PubMed Web of Science ®Google Scholar
• REINER JE, SIEV DV, ARALDI GL et al.:noncovalent thrombin inhibitors featuring p(3)-heterocycles with P(1)- monocyclic arginine surrogates. Bioorg. Med. Chem. Lett. (2002) 12:1203–1208.
   PubMedGoogle Scholar
• HANESSIAN S, BALAUX E, MUSIL D, OLSSON LL, NILSSON I: Exploring the chiral space within the active site of alpha-thrombin with a constrained mimic of D-Phe-Pro-Arg-design, synthesis, inhibitory activity and X-ray structure of an enzyme-inhibitor complex. Bioorg. Med. Chem. Lett. (2000) 10:243–247.
   PubMed Web of Science ®Google Scholar
• SHERRY S, ALKJAERSIG N, FLETCHER AP: Comparative activity of thrombin on substituted arginine and lysine esters. Am. Physiol (1965) 209:577–583.
   PubMedGoogle Scholar
• STURZEBECHER J, MARK WARDT F,VOIGT B, WAGNER G, WALSMANN P: Cyclic amides of N a-arylsulfonylaminoacylated 4-amidinophenylalanine-tight binding inhibitors of thrombin. Thromb. Res. (1983) 29:635–642.
   PubMedGoogle Scholar
• OKAMOTO S, KINJO K, HIJIKATA A et al.: Thrombin inhibitors. 1. Ester derivatives of N alpha-(arylsulfony1)-L-arginine. J. Med. Chem. (1980) 23:827–830.
   Google Scholar
• KIKUMOTO R, TAMAO Y, OHKUBO K et al.: Thrombin inhibitors. 2. Amide derivatives of N alpha-substituted L-arginine. J. Med. Chem. (1980) 23:830–836.
   Google Scholar
• KIKUMOTO R, TAMAO Y, OHKUBO K et al.: Thrombin inhibitors. 3. Carboxyl-containing amide derivatives of N alpha-substituted L-arginine. I Med. Chem. (1980) 23:1293–1299.
   Google Scholar
• BODE W, TURK D, STURZEBECHER J: Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha- (2-naphthyl-sulfonyl-glycy1)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl- 1- [N alpha- (3-methy1-1,2,3,4-tetrahydro-8- quinolinesulfony1)-L-arginy1]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP- thrombin and MQPA-thrombin. Eur.j Biochem. (1990) 193:175–182.
   Google Scholar
• ••The first X-ray structure of thrombin incomplex with a potent inhibitor (NAPAP) which was essential for the future drug design of most inhibitors in clinical development nowadays.
   Google Scholar
• BANNER DW, HADVARY P: Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors. Biol. Chem. (1991) 266:20085–20093.
   Google Scholar
• BRANDSTETTER H, TURK D, HOEFFKEN HW et al: Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics.Biol. (1992) 226:1085–1099.
   Google Scholar
• BANNER DW, HADVARY P: Inhibitor binding to thrombin: X-ray crystallographic studies. Adv. Exp. Med. Biol. (1993) 340:27–33.
   PubMedGoogle Scholar
• HILPERT K, ACKERMANN J, BANNER DW et al.: Design and synthesis of potent and highly selective thrombin inhibitors.' Med. Chem. (1994) 37:3889–3901.
   Google Scholar
• ZEGA A, MLINSEK G, SEPIC P et al.: Design and structure-activity relationship of thrombin inhibitors with an azaphenylalanine scaffold: potency and selectivity enhancements via P2 optimization. Bioorg. Med. Chem. (2001) 9:2745–2756.
   PubMedGoogle Scholar
• SANGS00 K, SANG YH, YOUNG KK, MIKYUNG Y, YEONG SO: Rational design of selective thrombin inhibitors. Bioorg. Med. Chem. Lett. (1997) 7:769–774.
   Google Scholar
• KOKKO KP, ARRIGONI CE, DIX TA: Selectivity enhancement induced by substitution of nonnatural analogues of arginine and lysine in arginine-based thrombin inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:1947–1950.
   PubMedGoogle Scholar
• ST LAURENT DR, BALASUBRAMANIAN N, HAN WT et al.: active site-directed thrombin inhibitors-II. Studies related to arginine/ guanidine bioisosteres. Bioorg. Med. Chem. (1995) 3:1145–1156.
   PubMedGoogle Scholar
• HAYLER J, KANE PD, LEGRAND D et al.: The design and synthesis of thrombin inhibitors: the introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors. Bioorg. Med. Chem. Lett. (2000) 10:1567–1570.
   PubMedGoogle Scholar
• LINUSSON A, GOTTFRIES J, OLSSON T et al.: Statistical molecular design, parallel synthesis and biological evaluation of a library of thrombin inhibitors. J. Med. Chem. (2001) 44:3424–3439.
   PubMedGoogle Scholar
• HAUEL NH, NAR H, PRIEPKE H, RIES U, STASSEN JM, WIENEN W: Structure-based design of novel potent nonpeptide thrombin inhibitors. J. Med. Chem (2002) 45:1757–1766.
   PubMed Web of Science ®Google Scholar
• QUAN ML, WEXLER RR: The design andsynthesis of noncovalent Factor Xa inhibitors. Can: Top. Med. Chem. (2001) 1:137–149.
   PubMedGoogle Scholar
• POST JM, SULLIVAN ME, ABENDSCHEIN D, EWING J, HINCHMANJVV, LIGHT DR Human in vitropharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031). Thromb. Res. (2002) 105:347–352.
   PubMed Web of Science ®Google Scholar
• LEADLEY RI, JR.: Coagulation Factor Xa inhibition: biological background and rationale. Curc Top. Med. Chem. (2001) 1:151–159.
   PubMedGoogle Scholar
• DYKE CK, BECKER RC, KLEIMAN NS et al.: First experience with direct Factor Xa inhibition in patients with stable coronary disease: a pharmacokinetic and pharmacodynamic evaluation. Circulation (2002) 105:2385–2391.
   PubMed Web of Science ®Google Scholar
• MCKENZIE CR, ABENDSCHEIN DR, EISENBERG PR: Sustained inhibition of whole-blood clot procoagulant activity by inhibition of thrombus-associated Factor Xa. Arterioscler. Thromb. Vasc. Biol. (1996) 16:1285–1291.
   PubMedGoogle Scholar
• KOTZE HF, LAMPRECHT S, BADENHORST PN, ROODT JP, VAN WYK V: Transient interruption of arterial thrombosis by inhibition of Factor Xa results in long-term antithrombotic effects in baboons. Thromb. Haemost. (1997) 77:1137–1142.
   PubMedGoogle Scholar
• ABENDSCHEIN DR, BAUM PK, VERHALLEN P, EISENBERG PR, SULLIVAN ME, LIGHT DR: A novel synthetic inhibitor of Factor Xa decreases early reocclusion and improves 24-h patency after coronary fibrinolysis in dogs. Pharmacol. Exp. Ther. (2001) 296:567–572.
   PubMedGoogle Scholar
• REBELLO SS, KASIEWSKI CJ, WANG111.W et al.: Role of short-term inhibition of Factor Xa by FXV673 in arterial passivation: a study in a chronic model of thrombosis in conscious dogs. Cardiovasc. Pharmacol. (2001) 38:288–297.
   Google Scholar
• WYSOKINSKI W, MCBANE R,112.CHESEBRO JH, OWEN WG: Reversibility of platelet thrombosis in vivo. Quantitative analysis in porcine carotid arteries. Thromb. Haemost. (1996) 76:1108–1113.
   Google Scholar
• MAIGNAN S, MIKOL V: The use of 3D structural data in the design of specific Factor Xa inhibitors. Can: Top. Med. Chem. (2001) 1:161–174.
   Google Scholar
• DOUGHERTY DA: Cation-pi interactions in chemistry and biology: a new view of benzene, Phe, Tyr and Trp. Science (1996) 271:163–168.
   PubMed Web of Science ®Google Scholar
• TIDWELL RR, WEBSTER WP, SHAVER SR, GERATZ JD: Strategies for anticoagulation with synthetic protease inhibitors. Xa inhibitors versus thrombin inhibitors. Thromb. Res. (1980) 19:339–349.
   Google Scholar
• STURZEBECHER J, STURZEBECHER U, VIEWEG H, WAGNER G, HAUPTMANN J, MARK WARDT F: Synthetic inhibitors of bovine Factor Xa and thrombin comparison of their anticoagulant efficiency. Thromb. Res. (1989) 54:245–252.
   PubMed Web of Science ®Google Scholar
• NAGAHARA T, YOKOYAMA Y, INAMURA K et al.: Dibasic (amidinoaryflpropanoic acid derivatives as novel blood coagulation Factor Xa inhibitors. J. Med. Chem. (1994) 37:1200–1207.
   PubMed Web of Science ®Google Scholar
• PORCARI AR, CHI L, LEADLEY R: Recent advances in clinical trials of the direct and indirect selective Factor Xa inhibitors. Expert Opin. Investig. Drugs (2000) 9:1595–1600.
   PubMed Web of Science ®Google Scholar
• TANIUCHI Y, SAKAI Y, HISAMICHI N et al.: Biochemical and pharmacological characterization of YM-60828, a newly synthesized and orally-active inhibitor of human Factor Xa. Thromb. Haemost. (1998) 79:543–548.
   PubMed Web of Science ®Google Scholar
• SATO K, KAWASAKI T, TANIUCHI Y, HIRAYAMA F, KOSHIO H, MATSUMOTO Y: YM-60828, a novel Factor Xa inhibitor: separation of its antithrombotic effects from its prolongation of bleeding time. Eui: Pharmacol. (1997) 339:141–146.
   PubMed Web of Science ®Google Scholar
• SATO K, KAWASAKI T, HISAMICHI N et al.: Antithrombotic effects of YM-60828, a newly synthesized Factor Xa inhibitor, in rat thrombosis models and its effects on bleeding time. Br. J. Pharmacol. (1998) 123:92–96.
   PubMed Web of Science ®Google Scholar
• HIRAYAMA F, KOSHIO H, KATAYAMA N et al: The discovery of YM-60828: a potent, selective and orally-bioavailable Factor Xa inhibitor. Bioorg. Med. Chem. (2002) 10:1509–1523.
   PubMed Web of Science ®Google Scholar
• PHILLIPS GB, BUCKMAN BO, DAVEY DD et al: Discovery of N- [2- [5- [Amino (imino)methyl]-2- hydroxyphenoxy1-3, 5- difluoro 6 [3 (4, 5 dihydro-l-methy1-1H-imidazol-2-y1)phenoxy]pyridin-4- yll-N-methylgl y cine (ZK-807834): a potent, selective and orally-active inhibitor of the blood coagulation enzyme Factor Xa. J. Med. Chem. (1998) 41:3557–3562.
   PubMed Web of Science ®Google Scholar
• ADLER M, DAVEY DD, PHILLIPS GB et al.: Preparation, characterization and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with Factor Xa. Biochemistry (2000) 39:12534–12542.
   PubMed Web of Science ®Google Scholar
• ABENDSCHEIN DR, BAUM PK, MARTIN DJ et al.: Effects of ZK-807834, a novel inhibitor of Factor Xa, on arterial and venous thrombosis in rabbits. Cardiovasc. Pharmacol. (2000) 35:796–805.
   PubMed Web of Science ®Google Scholar
• LIGHT DR, GUILFORD WW: Discovery of the Factor Xa inhibitor, ZK 807834 (CI-1031). Carr: Top. Med. Chem. (2001) 1:121–136.
   Google Scholar
• HEINELT U, HEROK S, MATTER H, WILDGOOSE P: Solid-phase optimisation of achiral amidinobenzyl indoles as potent and selective Factor Xa inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:227–230.
   PubMedGoogle Scholar
• SU T, WU Y, DOUGHAN B et al.: Design and synthesis of glycolic and mandelic acid derivatives as Factor Xa inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:2279–2282.
   PubMedGoogle Scholar
• SU T, WU Y, DOUGHAN Bet al.: Design, synthesis and SAR of amino acid derivatives as Factor Xa inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:2947–2950.
   Google Scholar
• PINTO DJ, ORWAT MJ, WANG S et al: Discovery of 1- [3- (aminomethyl)phenyl]-N-3-fluoro-2'- (methylsulfony1)- [1,1'-biphenyl] 4 yll 3 (trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective and orally bioavailable inhibitor of blood coagulation Factor Xa. J. Med. Chem. (2001) 44:566–578.
   PubMed Web of Science ®Google Scholar
• FEVIG JM, PINTO DJ, HAN Q et al: Synthesis and SAR of benzamidine Factor Xa inhibitors containing a vicinally-substituted heterocyclic core. Bioorg. Med. Chem. Lett. (2001) 11:641–645.
   PubMed Web of Science ®Google Scholar
• JONES SD, LIEBESCHUETZ JVV, MORGAN PJ et al.: The design of phenylglycine containing benzamidine carboxamides as potent and selective inhibitors of Factor Xa. Bioorg. Med. Chem. Lett. (2001) 11:733–736.
   PubMedGoogle Scholar
• LIEBESCHUETZ JVV, JONES SD, MORGAN PJ et al.: PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective Factor Xa inhibitors. Med. Chem. (2002) 45:1221–1232.
   Google Scholar
• RAI R, KOLESNIKOV A, LI Y et al.: Development of potent and selective Factor Xa inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:1797–1800.
   PubMedGoogle Scholar
• NISHIDA H, MIYAZAKI Y, KITAMURA Y et al: Synthesis and evaluation of 1-arylsulfony1-3-piperazinone derivatives as Factor Xa inhibitor. Chem. Pharm. Bull. (Tokyo) (2001) 49:1237–1244.
   PubMedGoogle Scholar
• EDWARDS PD: Human neutrophil elastase inhibitors. In: Protease and Peptidase Inhibition -Recent Potential Targets for Drug Development. Smith HJ, Simons C (Eds), Taylor & Francis, London & New York (2002):154–177.
   Google Scholar
• ••Excellent and exhaustive review on HNEinhibitors.
   Google Scholar
• AN-ZHI W, MAYR I, BODE W.:The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett (1988) 234:367–373.
   Google Scholar
• DE NANTEUIL G, PORTEVIN B, BENOIST A: Disease-modifying antiostheoarthritic drugs: current therapies and new prospects around protease inhibition. Farmaco (2001) 56:107–112.
   PubMedGoogle Scholar
• •Good review on the latest developments of protease inhibitors in clinical development.
   Google Scholar
• TOMIZAWA N, OHWADA S, OHYA T et al.: The effects of a neutrophil elastase inhibitor (ONO-5046 Na) and neutrophil depletion using a granulotrap (G-1) column on lung reperfusion injury in dogs. I Heart Lung Transplant. (1999) 18:637–645.
   PubMedGoogle Scholar
• KIRSCEHNHEUTER GP, OLEKSYSZYN J, LYLE W et al.: Synthesis and characterization of human neutrophil elastase inhibitors derived from aromatic esters of phenylalkanoic acids. Agents Act. (1993) 42:71–82.
   PubMedGoogle Scholar
• LUISETTI M, STURANI C, SELLA D et al.: MR889, a neutrophil elastase inhibitor, in patients with chronic pulmonary obstructive disease: a double-blind, randomized, placebo-controlled clinical trial. Eur. Resp. .1. (1996) 9:1482-1486.
   Google Scholar
• VEALE CA, BERNSTEIN PR, BOHNERT CM et al.: Orally-active trifluoromethyl ketone inhibitors of human leukocyte elastase. Med. Chem. (1997) 40:3173–3181.
   Google Scholar
• VINCENT SH, PAINTER SK, LUFFER-ATLAS D et al. Orally-active inhiibtors of human leukocyte elastase. II. Disposition of L-694,458 in rats and rhesus monkeys. Drug Metab. Dispos. (1997) 25:932–939.
   Google Scholar
• DUNBAR SD, ORNSTEIN DL, ZACHARSKI LR:Cancer treatment with inhibitors of urokinase-type plasminogen activator and plasmin. Exp. Opin. Investig. Drugs (2000) 9:2085–2092.
   PubMed Web of Science ®Google Scholar
• BURGLE M, SPERL S, STURZEBECHER J et al.: The urokinase-type plasminogen activator (uPA) system: a new target for tumour therapy. In: Protease and Peptidase Inhibition - Recent Potential Targets for Drug Development. Smith HJ, Simons C (Eds), Taylor & Francis, London and New York (2002):231–248.
   Google Scholar
• ••Very good and clearly written review onuPA inhibitors, from drug design to the pharmacological evaluation of this type of interesting derivatives.
   Google Scholar
• RABBANI SA, HARAKIDAS P, DAVIDSON DJ, HENKIN J, MAZAR AP: Prevention of prostate-cancer metastasis in vivo by a novel synthetic inhibitor of urokinase-type plasminogen activator (uPA). Int. J. Cancer (1995) 63:840–845.
   PubMed Web of Science ®Google Scholar
• SWIERCZ R, SKRZYPCZAK-JANKUN E, MERRELL MM, SELMAN SH, JANKUN J: Angiostatic activity of synthetic inhibitors of urokinase type plasminogen activator. Oncol Rep. (1999) 6:523–526.
   PubMed Web of Science ®Google Scholar
• SPRAGGON G, PHILLIPS C, NOWAK UK: The crystal structure of the catalytic domain of human urokinase-type plasminogen activator. Structure (1995) 15:681–691.
   Google Scholar
• KATZ BA, SPRENGELER PA, LUONG C et al.: Engineering inhibitors highly selective for the 51 sites of Ser190 trypsin-like serine protease drug targets. Chem. Biol. (2001) 8:1107–1121.
   PubMedGoogle Scholar
• MACKMAN RL, KATZ BA, BREITENBUCHER JG et al: Exploiting subsite 51 of trypsin-like serine proteases for selectivity: potent and selective inhibitors of urokinase-type plasminogen activator.' Med. Chem. (2001) 44:3856–3871.
   Google Scholar
• SPERL S, JACOB U, ARROYO DE PRADA N et al: (4-minomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase. Proc. Natl. Acad. Sci. USA (2000) 97:5113–5118.
   PubMed Web of Science ®Google Scholar
• BARBER CG, DICKINSON RP, HORNE VA: Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-Pyridinylguanidines. Bioorg. Med. Chem. Lett. (2002) 12:181–184.
   Google Scholar
• BARBER CG, DICKINSON RP: Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 2: (3-Substituted-5-halo-2-pyridinyl)guanidines. Bioorg. Med. Chem. Lett. (2002) 12:185–187.
   Google Scholar
• WILSON KJ, ILLIG CR, SUBASINGHE N et al.: Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:915–918.
   PubMed Web of Science ®Google Scholar
• SUBASINGHE NL, ILLIG C, HOFFMAN J et al.: Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:1379–1382.
   PubMedGoogle Scholar
• SOMMERHOFF CP, BODE W, MATSCHINER G, BERGNER A, FRITZ H: The human mast cell tryptase tetramer: a fascinating riddle solved by structure. Biochim. Biophys. Acta (2000) 1477:75–89.
   PubMed Web of Science ®Google Scholar
• STUBBS M, MORENWEISER R, STURZEBECHER J et al.: The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin - Implications for the structure of human mast cell tryptase and its inhibition. Biol. Chem. (1997) 272:19931–19937.
   Google Scholar
• ••X-ray structure determination of tryptase, which was essential for the development of strong inhibitors.
   Google Scholar
• RICE KD, TANAKA RD, KATZ BA, NUMEROF RP, MOORE WR: Inhibitors of tryptase for the treatment of mast cell-mediated diseases. Carr: Pharm. Des (1998) 4:381–396.
   PubMed Web of Science ®Google Scholar
• KATZ BA, CLARK JM, FINER-MOORE JS et al: Design of potent selective zinc-mediated serine protease inhibitors. Nature (1998) 391:608–612.
   PubMed Web of Science ®Google Scholar
• KRISHNA MT, CHAUHAN A, LITTLE L et al.: Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma. I Allergy Clin. Immunol (2001) 107:1039–1045.
   PubMed Web of Science ®Google Scholar
• WRIGHT CD, HAVILL AM, MIDDLETON Sc et al: Inhibition of allergen-induced pulmonary responses by the selective tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyl]-phenoxyl-pentane (AMG-126737). Biochem. Pharmacol (1999) 58:1989–1996.
   PubMed Web of Science ®Google Scholar
• RICE KD, GANGLOFF AR, KUO EY et al.: Dibasic inhibitors of human mast cell tryptase. Part 1: synthesis and optimization of a novel class of inhibitors. Bioorg. Med. Chem. Lett. (2000) 10:2357–2360.
   Google Scholar
• RICE KD, WANG VR, GANGL OFF AR et al.: Dibasic inhibitors of human mast cell tryptase. Part 2: structure-activity relationships and requirements for potent activity. Bioorg. Med. Chem. Lett. (2000) 10:2361–2366.
   Google Scholar
• ONO S, KUWAHARA S, TAKEUCHI M, SAKASHITA H, NAITO Y, KONDO T: Syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors. Bioorg. Med. Chem. Lett. (1999) 9:3285–3290.
   PubMed Web of Science ®Google Scholar
• SCHASCHKE N, MATSCHINER G, ZETTL F et al.: Bivalent inhibition of human 3-tryptase. Chem. Biol. (2001) 8:313–327.
   PubMedGoogle Scholar
• JANC JW, CLARK JM, WARNE RL, ELROD KC, KATZ BA, MOORE WR: A novel approach to serine protease inhibition: kinetic characterization of inhibitors whose potencies and selectivities are dramatically enhanced by zinc(II). Biochemistry (2000) 39:4792–4800.
   PubMedGoogle Scholar
• ERBA F, FIORUCCI L, PASCARELLA S, MENEGATTI E, ASCENZI P, ASCOLI F: Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiprotease drug. Biochem. Pharmacol (2001) 61:271–276.
   PubMed Web of Science ®Google Scholar
• DE CLERCQ E: Strategies in the design of antiviral drugs. Nat. Drug Des (2002) 1:13–25.
   PubMed Web of Science ®Google Scholar
• ••Excellent review on antivirals.
   Google Scholar
• RICHMAN DR: HIV chemotherapy. Nature (2001) 410:995–1001.
   PubMed Web of Science ®Google Scholar
• JARVEST RL, DABROWSKI CE: Herpesvirus and cytomegalovirus protease. In: Protease and Peptidase Inhibition - Recent Potential Targets for Drug Development. Smith HJ, Simons C (Eds), Taylor & Francis, London and New York (2002):264–281.
   Google Scholar
• RAWLINSON WD: Diagnosis of human cytomegalovirus infection and disease. Pathology (1999) 31:109–115.
   PubMed Web of Science ®Google Scholar
• ENSOLI B, STURZL M, MONINI P: Reactivation and role of HHV-8 in Kaposi's sarcoma initiation. Adv. Cancer Res. (2001) 81:125–159.
   PubMedGoogle Scholar
• RETTIG MB, MA HJ, VESCIO RA et al: Kaposi's sarcoma associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science (1998) 276:1851–1854.
   Google Scholar
• LIU F, ROIZMAN B: The HSV-1 gene encoding a protease also contains within its coding domain the gene encoding the more abundant substrate. J. Virol. (1991) 65:5149–5156.
   PubMedGoogle Scholar
• SHIEH HS, KURUMBAIL RG, STEVENS AM et al.: Three dimensional structure of human cytomegalovirus protease. Nature (1996) 383:279–282.
   PubMed Web of Science ®Google Scholar
• •The X-ray structure of the HCMV protease is reported in this paper.
   Google Scholar
• BORTHWICK AD, CRAME AJ, ERTL PF et al.: Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxohexahydropyrrolo [3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 2. Potency and chirality. J. Med. Chem. (2002) 45:1–18.
   Google Scholar
• •The first potent HCMV protease is reported in this paper.
   Google Scholar
• WALKER MA: Hepatitis C virus: an overview of current approaches and progress. Drug Dev. Today (1999) 4:518–529.
   PubMedGoogle Scholar
• PURCELL RH: Hepatitis C virus. Historical perspectives and current concepts. FEMS Microbiol Rev (1994) 14:181–192.
   PubMedGoogle Scholar
• CHOO QL, KUO G, VVEINER AJ et al: Genetic organization and diversity of hepatitis C virus. Proc. Natl Acad. ScL USA (1991) 88:2451–2455.
   PubMed Web of Science ®Google Scholar
• KIM JL, MORGENSTERN KA, LIN C et al.: Crystal structure of hepatitis C virus N53 protease domain complexed with a synthetic NS4A cofactor peptide. Cell (1996) 87:343–355.
   PubMed Web of Science ®Google Scholar
• BARTENSCHLAGER R, KOCH JO: The hepatitis C virus NS-3 serine-type protease. In: Protease and Peptidase Inhibition - Recent Potential Targets for Drug Development, Smith HJ, Simons C (Eds), Taylor & Francis, London and New York (2002):333–351.
   Google Scholar
• INGALLINELLA P, FATTORI D, ALTAMURA S et al: Prime site inhibitors of a serine protease: N53/4A of hepatitis C virus. Biochemistry (2002) 41:5483–5492.
   PubMed Web of Science ®Google Scholar
• •Potent and structurally novel inhibitors of the NS3 HCV protease are reported.
   Google Scholar
• YEUNG KS, MEANWELL NA, QIU Z et al.: Structure-activity relationship studies of bisbenzimidazole-based Zn2+-dependent inhibitor of HCV N53 serine protease. Bioorg. Med. Chem. Lett. (2001) 11:2355–2359.
   PubMedGoogle Scholar
• Dalbey RE: Signal peptidase I. In: Handbook of Proteolytic Enzymes (cd-rom); Barett AJ, Rawlings ND, WoessnerJF Jr., (Eds), Academic Press, London (1998):chapter 153.
   Google Scholar
• STEIN RL, BARBOSA MD, BRUCKNER R: Kinetic and mechanistic studies of signal peptidase I from Escherichia Biochemistry (2000) 39:7973–7983.
   Google Scholar
• ALLSOP AE, BROOKS G, BRUTON G et al.: Penem inhibitors of bacterial signal peptidase. Bioorg. Med. Chem. Lett. (1995) 5:443–448.
   Web of Science ®Google Scholar
• PETITOU M, DUCHAUSSOY P, JAURAND G et al.: Synthesis and pharmacological properties of a close analogue of an antithrombotic pentasaccharide (SR 90107A/ORG 31540). [Med Chem. (1997) 40:1600–1607.
   Google Scholar
• TURPIE AG: Pentasaccharide Org31540/ 5R90107A clinical trials update: lessons for practice. Am. Heart J. (2001) 142:9–15.
   Google Scholar
• TURPIE AG, GALLUS AS, HOEK JA: A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl. J. Med. (2001) 344:619–625.
   PubMed Web of Science ®Google Scholar
• HERZOG RW, HIGH KA: Ad.-associated virus-mediated gene transfer of Factor IX for treatment of hemophilia B by gene therapy. Thromb. Haemost. (1999) 82:540–546.
   Google Scholar
• GREENGARD JS, JOLLY DJ: Animal testing of retroviral-mediated gene therapy for Factor VIII deficiency. Thromb. Haemost. (1999) 82:555–561.
   PubMed Web of Science ®Google Scholar
• GERARD RD, COLLEN D: Adenovirus gene therapy for hypercholesterolemia, thrombosis and restenosis. Cardiovasc. Res. (1997) 35:451–458.
   PubMed Web of Science ®Google Scholar
• ILIES MA, BALABAN AT: Recent developments in cationic lipid-mediated gene delivery and gene therapy. 11:1729–1752.
   Google Scholar
• MAURER N, FENSKE DB, CULLIS PR: Developments in liposomal drug delivery systems. Expert Opin. Biolog. Ther: (2001) 1:923–947.
   PubMed Web of Science ®Google Scholar
• FIELDS PA, PAST KJ: Gene therapy for haemophilia: how far have we come? Haemophilia (1998) 4:699–703.
   PubMedGoogle Scholar
• CONNELLY S, KALEKO M: Haemophilia A gene therapy. Haemophilia (1998) 4:380–388.
   PubMedGoogle Scholar
• VASSALLI G, DICHEK DA: Gene therapy for arterial thrombosis. Cardiovasc. Res. (1997) 35:459–469.
   PubMedGoogle Scholar
• BRUGADA R, ROBERTS R: Gene therapy for cardiovascular diseases. Expert Opin. Ther. Patents (2000) 10:1385–1393.
   Web of Science ®Google Scholar
• QUARCK R, HOLVOET P: Restenosis and gene therapy. Expert Opin. Biol. The]: (2001) 1:79–91.
   PubMed Web of Science ®Google Scholar
• FACTOR P: Gene therapy for acute diseases. MM. Ther: (2001) 4:515–524.
   PubMedGoogle Scholar