1tu6 › Citations

Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions.

Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Shewchuk LM, Wells-Knecht KJ, Willard DH, Wright LL
Bioorg Med Chem Lett 14 4897-902 (2004)
Cited: 17 times
EuropePMC logo PMID: 15341947

Abstract

A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors.

Articles - 1tu6 mentioned but not cited (5)

  1. A system-level investigation into the mechanisms of Chinese Traditional Medicine: Compound Danshen Formula for cardiovascular disease treatment. Li X, Xu X, Wang J, Yu H, Wang X, Yang H, Xu H, Tang S, Li Y, Yang L, Huang L, Wang Y, Yang S. PLoS One 7 e43918 (2012)
  2. The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma. Newton GK, Perrior TR, Jenkins K, Major MR, Key RE, Stewart MR, Firth-Clark S, Lloyd SM, Zhang J, Francis-Newton NJ, Richardson JP, Chen J, Lai P, Garrod DR, Robinson C. J Med Chem 57 9447-9462 (2014)
  3. Spectroscopic and computational investigation of three Cys-to-Ser mutants of nickel superoxide dismutase: insight into the roles played by the Cys2 and Cys6 active-site residues. Johnson OE, Ryan KC, Maroney MJ, Brunold TC. J Biol Inorg Chem 15 777-793 (2010)
  4. On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors. Bonatto V, Batista PHJ, Cianni L, De Vita D, Silva DG, Cedron R, Tezuka DY, de Albuquerque S, Moraes CB, Franco CH, Lameira J, Leitão A, Montanari CA. RSC Med Chem 11 1275-1284 (2020)
  5. Inverse Mixed-Solvent Molecular Dynamics for Visualization of the Residue Interaction Profile of Molecular Probes. Yanagisawa K, Yoshino R, Kudo G, Hirokawa T. Int J Mol Sci 23 4749 (2022)


Reviews citing this publication (3)

  1. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Brömme D, Lecaille F. Expert Opin Investig Drugs 18 585-600 (2009)
  2. Biochemical properties and regulation of cathepsin K activity. Lecaille F, Brömme D, Lalmanach G. Biochimie 90 208-226 (2008)
  3. Recent applications of protein crystallography and structure-guided drug design. Williams SP, Kuyper LF, Pearce KH. Curr Opin Chem Biol 9 371-380 (2005)

Articles citing this publication (9)

  1. P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K. Barrett DG, Boncek VM, Catalano JG, Deaton DN, Hassell AM, Jurgensen CH, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA, Ray JA, Samano V, Shewchuk LM, Tavares FX, Wells-Knecht KJ, Willard DH, Wright LL, Zhou HQ. Bioorg Med Chem Lett 15 3540-3546 (2005)
  2. Reactivity change of cyclobutanols towards isocyanates: rhodium favors C-carbamoylation over O-carbamoylation. Ishida N, Nakanishi Y, Murakami M. Angew Chem Int Ed Engl 52 11875-11878 (2013)
  3. 3D QSAR studies on ketoamides of human cathepsin K inhibitors based on two different alignment methods. Pan X, Tan N, Zeng G, Huang H, Yan H. Eur J Med Chem 45 667-681 (2010)
  4. Novel acetamidothiazole derivatives: synthesis and in vitro anticancer evaluation. Ali AR, El-Bendary ER, Ghaly MA, Shehata IA. Eur J Med Chem 69 908-919 (2013)
  5. Ketoheterocycle-based inhibitors of cathepsin K: a novel entry into the synthesis of peptidic ketoheterocycles. Tavares FX, Deaton DN, Miller AB, Miller LR, Wright LL. Bioorg Med Chem Lett 15 3891-3895 (2005)
  6. 4-Aminophenoxyacetic acids as a novel class of reversible cathepsin K inhibitors. Shinozuka T, Shimada K, Matsui S, Yamane T, Ama M, Fukuda T, Taki M, Naito S. Bioorg Med Chem Lett 16 1502-1505 (2006)
  7. Novel, potent P2-P3 pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors. Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Ray JA, Samano V, Shewchuk LM, Wells-Knecht KJ, Willard DH, Wright LL. Bioorg Med Chem Lett 16 1735-1739 (2006)
  8. 3D-QSAR and docking studies of aldehyde inhibitors of human cathepsin K. Pan X, Tan N, Zeng G, Han H, Huang H. Bioorg Med Chem 14 2771-2778 (2006)
  9. Theoretical studies on the interaction between the nitrile-based inhibitors and the catalytic triad of Cathepsin K. Pitchumani Violet Mary C, Shankar R, Vijayakumar S. J Biomol Struct Dyn 36 634-655 (2018)


Quick links