Selective inhibitors of fibroblast activation protein (FAP) with a (4-quinolinoyl)-glycyl-2-cyanopyrrolidine scaffold

ACS Medicinal Chemistry Letters

Volumn 4, Issue 5, 2013, Pages 491-496

  Jansen, Koen ^a   Heirbaut, Leen ^a   Cheng, Jonathan D ^b   Joossens, Jurgen ^a   Ryabtsova, Oxana ^a   Cos, Paul ^a   Maes, Louis ^a   Lambeir, Anne Marie ^a   De Meester, Ingrid ^a   Augustyns, Koen ^a   Van Der Veken, Pieter ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b FOX CHASE CANCER CENTER   (United States)

Author keywords

dipeptidyl peptidase IV (DPPIV); Fibroblast activation protein (FAP); prolyl oligopeptidase (PREP); seprase

Indexed keywords

ANTINEOPLASTIC AGENT; DIPEPTIDYL PEPTIDASE; N (4 QUINOLINOYL) GLY (2 CYANOPYRROLIDINE); NITROGEN; PROLYL ENDOPEPTIDASE; PYRROLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG BLOOD LEVEL; DRUG SCREENING; KINETICS; MOLECULAR STABILITY; PRIORITY JOURNAL; SOLUBILITY; STRUCTURE ACTIVITY RELATION;

EID: 84877712854     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml300410d     Document Type: Article

References (28)

1. Aertgeerts, K.; Levin, I.; Shi, L.; Snell, G. P.; Jennings, A.; Prasad, G. S.; Zhang, Y.; Kraus, M. L.; Salakian, S.; Sridhar, V.; Wijnands, R.; Tennant, M. G. Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha J. Biol. Chem. 2005, 280, 19441-19444
2. Garin-Chesa, P.; Old, L. J.; Rettig, W. J. Cell-surface protein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 7235-9
3. Scanlan, M. J.; Raj, B. K.; Calvo, B.; Garin-Chesa, P.; Sanz-Moncasi, M. P.; Healey, J. H.; Old, L. J.; Rettig, W. J. Molecular cloning of fibroblast activation protein-alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 5657-5661
4. Santos, A. M.; Jung, J.; Aziz, N.; Kissil, J. L.; Puré, E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice J. Clin. Invest. 2009, 119, 3613-25
5. Cheng, J. D.; Valianou, M.; Canutescu, A. A.; Jaffe, E. K.; Lee, H. O.; Wang, H.; Lai, J. H.; Bachovchin, W. W.; Weiner, L. M. Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth Mol. Cancer Ther 2005, 4, 351-360
6. Wang, X. M.; Yao, T.-W.; Nadvi, N. A.; Osborne, B.; McCaughan, G. W.; Gorrell, M. D. Fibroblast activation protein and chronic liver disease Front. Biosci. 2008, 13, 3168-3180
7. Acharya, P. S.; Zukas, A.; Chandan, V.; Katzenstein, A. L.; Pure, E. Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis Hum. Pathol. 2006, 37, 352-360
8. Dienus, K.; Bayat, A.; Gilmore, B. F.; Seifert, O. Increased expression of fibroblast activation protein-alpha: implications for the development of a new treatment option Arch. Dermatol. Res. 2010, 302, 725-731
9. Milner, J. M.; Kevorkian, L.; Young, D. A.; Jones, D.; Wait, R.; Donell, S. T.; Barksby, E.; Patterson, A. M.; Middleton, J.; Cravatt, B. F.; Clark, I. M.; Rowan, A. D.; Cawston, T. Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis Arthritis Res. Ther. 2006, 8, R23
10. Milner, M.; Patel, A.; Rowan, A. D. Emerging role of serine proteinases in tissue turnover in arthritis Arthritis Rheum. 2008, 58, 3644-3656
11. Bauer, S.; Jendro, M. C.; Wadle, A.; Kleber, S.; Stenner, F.; Dinser, R.; Reich, A.; Faccin, E.; Gödde, S.; Dinges, H.; Müller-Ladner, U.; Renner, C. Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes Arthritis Res. Ther. 2006, 8, R171
12. Brokopp, C. E.; Schoenauer, R.; Richards, P.; Bauer, S.; Lohmann, C.; Emmert, M. Y.; Weber, B.; Winnik, S.; Aikawa, E.; Graves, K.; Genoni, M.; Vogt, P.; Lüscher, T. F.; Renner, C.; Hoerstrup, S. P.; Matter, C. M. Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheroma Eur. Heart J. 2011, 32, 2713-2722
13. O'Brien, P.; O'Connor, B. F. Seprase: an overview of an important matrix serine protease Biochim. Biophys. Acta 2008, 1784, 1130-1145
14. Keane, F. M.; Nadvi, N. A.; Yao, T.-W.; Gorrell, M. D.; Neuropeptide, Y. B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-alpha FEBS J. 2011, 278, 1326-1332
15. Wolf, B. B.; Quan, C.; Tran, T.; Wiesman, C.; Sutherlin, C. On the edge of vamidation-Cancer protease fibroblast activation protein Mini-Rev. Med. Chem. 2008, 8, 719-727
16. Hu, Y.; Ma, L.; Wu, M.; Wong, M. S.; Li, B.; Corral, S.; Yu, Z.; Nomanbhoy, T.; Alemayehu, S.; Fuller, S. R.; Rosenblum, J. S.; Rozenkrants, N.; Minimo, L. C.; Ripka, W. C.; Szardenings, A. K.; Kozarich, J. W.; Shreder, K. R. Synthesis and structure-activity relationship of N-alkyl-Gly- boro Pro inhibitors Bioorg. Med. Chem. Lett. 2005, 15, 4239-4242
17. Eager, R. M.; Cunningham, C. C.; Senzer, N. N.; Stephenson, J.; Anthony, S. P.; O'Day, S. J.; Frenette, G.; Pavlick, A. C.; Jones, B.; Uprichard, M. Nemunaitis, Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma J BMC Cancer 2009, 9, 263
18. Narra, K.; Mullins, S. R.; Lee, H. O.; Stzremkowski-Brun, R.; Magalong, K.; Christansen, V. J.; McKee, P. A.; Egleston, B.; Cohen, S. J.; Weiner, L. M.; Meropol, N. J.; Cheng, J. D. Phase II trial of single agent Val-boroPro (talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer Cancer Biol. Ther. 2007, 7, 1691-1699
19. Ryabtsova, O.; Jansen, K.; Van Goethem, S.; Joossens, J.; Cheng, J. D.; Lambeir, A.-M.; De Meester, I.; Augustyns, K.; Van der Veken, P. Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity Bioorg. Med. Chem. Lett. 2012, 22, 3412-3417
20. Tsai, T. Y.; Yeh, T. K.; Chen, X.; Hsu, T.; Jao, Y. C.; Huang, C. H.; Song, J. S.; Huang, Y. C.; Chien, C. H.; Chiu, Y. H.; Yen, S. C.; Tang, H. K.; Chao, Y. S.; Jiaang, W. K. Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein J. Med. Chem. 2010, 53, 6573-6583
21. Villhauer, E. B.; Brinkman, J. A.; Naderi, G. B.; Burkey, B. F.; Dunning, B. E.; Prasad, K.; Mangold, B. L.; Russell, M. E.; Hughes, T. E. 1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties J. Med. Chem. 2003, 46, 2774-2789
22. Augeri, D. J.; Robl, J. A.; Betebenner, D. A.; Magnin, D. R.; Khanna, A.; Robertson, J. G.; Wang, A.; Simpkins, L. M.; Taunk, P.; Huang, Q.; Han, S. P.; Abboa-Offei, B.; Cap, M.; Xin, L.; Tao, L.; Tozzo, E.; Welzel, G. E.; Egan, D. M.; Marcinkeviciene, J.; Chang, S. Y.; Biller, S. A.; Kirby, M. S.; Parker, R. A.; Hamann, L.G. S. Synthesis of novel potent dipeptidyl peptidase IV Inhibitors with enhanced chemical stability: interplay between the N-terminal amino acid alkyl side chain and the cyclopropyl group of α-aminoacyl- l-cis -4,5-methanoprolinenitrile-based inhibitors J. Med. Chem. 2004, 47, 2587-2598
23. Ashworth, D. A.; Atrash, B.; Baker, G. A.; Baxter, A. J.; Jenkins, P. D.; Jones, M. D.; Szelke, M. 4-Cyanothiazolidides as very potent, stable inhibitors of dipeptidyl peptidase IV Bioorg. Med. Chem. Lett. 1996, 6, 1163
24. Van der Veken, P.; Haemers, A.; Augustyns, K. Prolyl peptidases related to dipeptidyl peptidase IV: Potential of specific inhibitors in drug discovery Curr. Top. Med. Chem. 2007, 7, 621-635
25. Thomas, L.; Eckhardt, M.; Langkopf, E.; Mark, M.; Tadayyon, M.; Thomas, L.; Nar, H.; Pfrengle, W.; Guth, B.; Lotz, R.; Sieger, P.; Fuchs, H.; Himmelsbach, F. 8-(3-(R)-Aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl- quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes J. Med. Chem. 2007, 50, 6450-6453
26. Van Goethem, S.; Mateeussen, V.; Joossens, J.; Lambeir, A. M.; Chen, X.; De Meester, I.; Haemers, A.; Augustyns, K.; Van der Veken, P. Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 8 (DPP8, DPP9): is DPP8-selectivity attainable? J. Med. Chem. 2011, 54, 5737-5746
27. Dubois, V.; Van Ginneken, C.; De Cock, H.; Lambeir, A. M.; Van der Veken, P.; Augustyns, K.; Chen, X.; Scharpe, S.; De Meester, I. Enzyme activity and immunohistochemical localization of dipeptidyl peptidase 8 and 9 in male reproductive tissues J. Histochem. Cytochem. 2009, 57, 531-541
28. Tran, T.; Quan, C.; Edosada, C. Y.; Mayeda, M.; Wiesmann, C.; Sutherlin, D.; Wolf, B. B. Synthesis and structure-activity relationship of N-acyl-Gly-, N-acyl-Sar- and N-blocked-boroPro inhibitors of FAP, DPP4 and POP Bioorg. Med. Chem. Lett. 2007, 17, 1438-1442