The Design of Synthetic Inhibitors of Thrombin

The Rational Design of Thrombin-Directed Antithrombotics.- X-Ray Crystal Structures of Thrombin in Complex with D-Phe-Pro-Arg and with Small Benzamidine and Arginine-Based "Non-Peptidic" Inhibitors.- Inhibitor Binding to Thrombin: X-Ray Crystallographic Studies.- Molecular Basis for the Inhibition of Thrombin by Hirudin.- Biophysical Studies of Interactions of Hirudin Analogs with Bovine and Human Thrombin by ESR and Fluorescence Labelling Studies.- pH-Dependent Binding Constants for the Inhibition of Thrombin by Transition State Analogues.- The Comparison of an Interim Tertiary Predicted Model of Bovine Thrombin and the X-Ray Structure of Human Thrombin.- Design of Novel Types of Thrombin Inhibitors Based on Modified D-Phe-Pro-Arg sequences.- Chemistry and Biology of the Peptide Anticoagulant D-MePhe-Pro-Arg-H (GYKI-14766).- Peptide Boronic Acid Inhibitors of Thrombin.- In Vitro and In Vivo Properties of Synthetic Inhibitors of Thrombin: Recent Advances.- The Use of Isosteric Bonds in the Design of Thrombin Inhibitors.- Synthetic Thrombin Inhibitors as Anticoagulants Pharmacological Aspects.- New Peptide Boronic Acid Inhibitors of Thrombin.- Substrate-Related Phosphonopeptides as Thrombin Inhibitors.- The Synthesis and Anticoagulant Activity of Novel Peptidylfluoroalkanes.- Transition State Analogue Inhibitors of Thrombin: Synthesis Activity and Molecular Modelling.- Hirudin: The Famous Anticoagulant Agent.- Mechanisms for the Anticoagulant Effects of Synthetic Antithrombins.- Pre-Clinical and Clinical Studies on Hirulog: A Potent and Specific Direct Thrombin Inhibitor.- The Effect of Recombinant Hirudin on Arterial Thrombosis.

[1]  S. Sherry,et al.  The action of thrombin on synthetic substrates. , 1954, The Journal of biological chemistry.

[2]  M. Blombäck,et al.  Synthetic peptides with anticoagulant and vasodilating activity. , 1969, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[3]  M. Weinstein,et al.  Differential specificities of the thrombin, plasmin and trypsin with regard to synthetic and natural substrates and inhibitors. , 1972, Biochimica et biophysica acta.

[4]  R. Kikumoto,et al.  Kinetic Studies on the Selectivity of a Synthetic Thrombin-Inhibitor Using Synthetic Peptide Substrates , 1979, Thrombosis and Haemostasis.

[5]  Comparison of plasma levels and excretory routes between No. 189 and No. 407, potent thrombin inhibitors. , 1980, The Kobe journal of medical sciences.

[6]  F. Markwardt,et al.  Anticoagulant and Antithrombotic Action of Novel Specific Inhibitors of Thrombin , 1980, Thrombosis and Haemostasis.

[7]  F. Markwardt,et al.  Adrenaline-induced reactions of human platelets in hirudin plasma. , 1980, Haemostasis.

[8]  T. Tezuka,et al.  Thrombin inhibitors. 3. Carboxyl-containing amide derivatives of N alpha-substituted L-arginine. , 1980, Journal of medicinal chemistry.

[9]  A novel series of synthetic thrombin-inhibitors. II. Relationships between structure of modified OM-inhibitors and thrombin inhibitory effect. , 1980, The Kobe journal of medical sciences.

[10]  R. Kikumoto,et al.  Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion. , 1981, Biochemical and biophysical research communications.

[11]  Y. Abiko,et al.  Comparative study on heparin and a synthetic thrombin inhibitor no. 805 (MD-805*) in experimental antithrombin III-deficient animals. , 1981, Thrombosis research.

[12]  Pharmacology of benzamidine-type thrombin inhibitors. , 1982, Folia haematologica.

[13]  Y. Shimada,et al.  APPLICATION OF HPLC MEASUREMENT OF PLASMA OF GABEXATE MESILATE CONCENTRATION , 1983 .

[14]  R. Kikumoto,et al.  Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl++ +) sulfonyl]-l-arginyl)]-2-piperidinecarboxylic acid. , 1984, Biochemistry.

[15]  F. Markwardt,et al.  Inhibition of the thrombin-platelet reaction by hirudin. , 1984, Haemostasis.

[16]  F. Markwardt,et al.  Pharmacokinetics and Anticoagulant Effect of Hirudin in Man , 1984, Thrombosis and Haemostasis.

[17]  R. Bizios,et al.  Thrombin-induced aggregation of lymphocytes: non-enzymic induction by an hirudin-blocked thrombin exosite. , 1985, Thrombosis research.

[18]  H. Taguchi,et al.  Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. , 1986, The Biochemical journal.

[19]  R. Kikumoto,et al.  Effect of a Selective Thrombin Inhibitor MCI-9038 on Fibrinolysis In Vitro and In Vivo , 1986, Thrombosis and Haemostasis.

[20]  Aromatic tetra-amidines: antiproteolytic and antiesterolytic activities towards serine proteinases involved in blood coagulation and clot lysis. , 1986, Il Farmaco; edizione scientifica.

[21]  S. Mao,et al.  Antithrombin properties of C‐terminus of hirudin using synthetic unsulfated N α‐acetyl‐hirudin45–65 , 1987, FEBS letters.

[22]  F. Markwardt,et al.  Effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III in thrombin-induced disseminated intravascular coagulation in rats. , 1987, Haemostasis.

[23]  F. Markwardt,et al.  Pharmacokinetic studies with recombinant hirudin in dogs. , 1988, Folia haematologica.

[24]  J. Hofsteenge,et al.  Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. , 1988, Biochemistry.

[25]  F. Markwardt,et al.  Clinico-pharmacological studies with recombinant hirudin. , 1988, Thrombosis research.

[26]  Studies on thrombin-induced endothelium-dependent vascular effects. , 1988, Biomedica biochimica acta.

[27]  S. Kobayashi,et al.  Effects of an antithrombotic agent (MD-805) on progressing cerebral thrombosis. , 1989, Thrombosis research.

[28]  W. Feinberg,et al.  Hemostatic markers in acute stroke. , 1989, Stroke.

[29]  C. Roitsch,et al.  Point mutations modifying the thrombin inhibition kinetics and antithrombotic activity in vivo of recombinant hirudin. , 1989, Protein engineering.

[30]  R. Peters,et al.  Recombinant Desulphatohirudin (CGP 39393) Anticoagulant and Antithrombotic Properties In Vivo , 1989, Thrombosis and Haemostasis.

[31]  F. Markwardt,et al.  Studies on antithrombotic effects of recombinant hirudin. , 1989, Thrombosis research.

[32]  M. Reboud-Ravaux,et al.  Reaction of thrombin and proteinases of the fibrinolytic system with a mechanism-based inhibitor, 3,4-dihydro-3-benzyl-6-chloromethylcoumarin. , 1990, Biochimica et biophysica acta.

[33]  J. Maraganore,et al.  Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. , 1990, Biochemistry.

[34]  Recombinant hirudin as an antithrombotic drug: current status and future perspectives , 1990 .

[35]  T. Lindhout,et al.  The Anticoagulant Mechanism of Action of Recombinant Hirudin (CGP 39393) in Plasma , 1990, Thrombosis and Haemostasis.

[36]  F. Markwardt,et al.  Platelet functions in recombinant hirudin-anticoagulated blood. , 1990, Haemostasis.

[37]  J. Hofsteenge,et al.  Use of fragments of hirudin to investigate thrombin-hirudin interaction. , 1990, European journal of biochemistry.

[38]  G. Nowak.  Pharmacokinetics of hirudin. , 1991, Seminars in thrombosis and hemostasis.

[39]  The comeback of hirudin as an antithrombotic agent. , 1991, Seminars in thrombosis and hemostasis.

[40]  E. Glusa.  Hirudin and Platelets , 1991, Seminars in thrombosis and hemostasis.