2a2x › Citations

Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety.

Lange UE, Baucke D, Hornberger W, Mack H, Seitz W, Höffken HW
Bioorg Med Chem Lett 16 2648-53 (2006)
Related entries: 2ank, 2anm

Cited: 14 times
EuropePMC logo PMID: 16460939

Abstract

Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration.

Reviews - 2a2x mentioned but not cited (1)

  1. Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands. Troisi R, Balasco N, Autiero I, Vitagliano L, Sica F. Int J Mol Sci 22 10803 (2021)

Articles - 2a2x mentioned but not cited (2)

  1. Structure-based predictions of activity cliffs. Husby J, Bottegoni G, Kufareva I, Abagyan R, Cavalli A. J Chem Inf Model 55 1062-1076 (2015)
  2. An evaluation of pharmacological healing potentialities of Terminalia Arjuna against several ailments on experimental rat models with an in-silico approach. Tahsin MR, Sultana A, Mohtasim Khan MS, Jahan I, Mim SR, Tithi TI, Ananta MF, Afrin S, Ali M, Hussain MS, Chowdhury JA, Kabir S, Chowdhury AA, Amran MS, Aktar F. Heliyon 7 e08225 (2021)


Reviews citing this publication (2)

  1. Direct thrombin inhibitors: patents 2002-2012 (Review). Kong Y, Chen H, Wang YQ, Meng L, Wei JF. Mol Med Rep 9 1506-1514 (2014)
  2. Advances in the synthesis of α-quaternary α-ethynyl α-amino acids. Boibessot T, Bénimélis D, Meffre P, Benfodda Z. Amino Acids 48 2081-2101 (2016)

Articles citing this publication (9)

  1. General and scalable amide bond formation with epimerization-prone substrates using T3P and pyridine. Dunetz JR, Xiang Y, Baldwin A, Ringling J. Org Lett 13 5048-5051 (2011)
  2. The marriage of organocatalysis with metal catalysis: access to multisubstituted chiral 2,5-dihydropyrroles by cascade iminium/enamine-metal cooperative catalysis. Sun W, Zhu G, Hong L, Wang R. Chemistry 17 13958-13962 (2011)
  3. Asymmetric organocatalytic allylic substitution of Morita-Baylis-Hillman carbonates with allylamines for the synthesis of 2,5-dihydropyrroles. Sun W, Ma X, Hong L, Wang R. J Org Chem 76 7826-7833 (2011)
  4. Catalytic synthesis of nonracemic azaproline derivatives by cyclization of β-alkynyl hydrazines under kinetic resolution conditions. Maity P, Lepore SD. Angew Chem Int Ed Engl 50 8338-8341 (2011)
  5. Discovery of potent, selective 4-fluoroproline-based thrombin inhibitors with improved metabolic stability. Staas DD, Savage KL, Sherman VL, Shimp HL, Lyle TA, Tran LO, Wiscount CM, McMasters DR, Sanderson PE, Williams PD, Lucas BJ, Krueger JA, Lewis SD, White RB, Yu S, Wong BK, Kochansky CJ, Anari MR, Yan Y, Vacca JP. Bioorg Med Chem 14 6900-6916 (2006)
  6. Enantioselective organocatalytic one-pot amination/aza-Michael/aldol condensation reaction sequence: synthesis of 3-pyrrolines with a quaternary stereocenter. Desmarchelier A, Coeffard V, Moreau X, Greck C. Chemistry 18 13222-13225 (2012)
  7. Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Mack H, Baucke D, Hornberger W, Lange UE, Seitz W, Höffken HW. Bioorg Med Chem Lett 16 2641-2647 (2006)
  8. Limiting the Number of Potential Binding Modes by Introducing Symmetry into Ligands: Structure-Based Design of Inhibitors for Trypsin-Like Serine Proteases. Furtmann N, Häußler D, Scheidt T, Stirnberg M, Steinmetzer T, Bajorath J, Gütschow M. Chemistry 22 610-625 (2016)
  9. Synthesis of functionalized 2,5-dihydropyrrole derivatives via a convenient [3 + 2] annulation of azomethine ylides with allenoates. Huang Z, Dai Z, Zhu J, Yang F, Zhou Q. Org Biomol Chem 16 6638-6646 (2018)


Quick links