Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors.
Drug Design
Enzyme Assays
Humans
Hydrogen Bonding
Immediate-Early Proteins
/ antagonists & inhibitors
Indazoles
/ chemical synthesis
Molecular Docking Simulation
Molecular Structure
Protein Binding
Protein Kinase Inhibitors
/ chemical synthesis
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Receptor, TIE-2
/ antagonists & inhibitors
Small Molecule Libraries
/ chemical synthesis
Structure-Activity Relationship
src-Family Kinases
/ antagonists & inhibitors
docking
drug design
focused library
kinase inhibition
nitrogen heterocycles
scaffolds
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
20 08 2019
20 08 2019
Historique:
received:
01
06
2019
revised:
26
06
2019
pubmed:
3
7
2019
medline:
1
9
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza-2H-indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC
Identifiants
pubmed: 31264364
doi: 10.1002/cmdc.201900328
doi:
Substances chimiques
Immediate-Early Proteins
0
Indazoles
0
Protein Kinase Inhibitors
0
Small Molecule Libraries
0
Receptor, TIE-2
EC 2.7.10.1
TEK protein, human
EC 2.7.10.1
src-Family Kinases
EC 2.7.10.2
Protein Serine-Threonine Kinases
EC 2.7.11.1
serum-glucocorticoid regulated kinase
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1514-1527Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
B. Klebl, G. Müller, M. Hamacher, Protein Kinases as Drug Targets, Wiley-VCH, Weinheim, 2011;
L. D. Wood, D. W. Parsons, S. Jones, J. Lin, T. Sjöblom, R. J. Leary, D. Shen, S. M. Boca, T. Barber, J. Ptak, N. Silliman, S. Szabo, Z. Dezso, V. Ustyanksky, T. Nikolskaya, Y. Nikolsky, R. Karchin, P. A. Wilson, J. S. Kaminker, Z. Zhang, R. Croshaw, J. Willis, D. Dawson, M. Shipitsin, J. K. V. Willson, S. Sukumar, K. Polyak, B. H. Park, C. L. Pethiyagoda, P. V. K. Pant, D. G. Ballinger, A. B. Sparks, J. Hartigan, D. R. Smith, E. Suh, N. Papadopoulos, P. Buckhaults, S. D. Markowitz, G. Parmigiani, K. W. Kinzler, V. E. Velculescu, B. Vogelstein, Science 2007, 318, 1108-1113.
P. Wu, T. E. Nielsen, M. H. Clausen, Trends Pharmacol. Sci. 2015, 36, 422-439.
FDA-approved small-molecule protein kinase inhibitors, compiled by Robert Roskoski, Jr.: http://www.brimr.org/PKI/PKIs.htm (accessed July 9, 2019).
H. M. Kantarjian, F. Giles, A. Quintás-Cardama, J. Cortes, Clin. Cancer. Res. 2007, 13, 1089-1097.
“Kinase-Centric Computational Drug Development”, A. J. Kooistra, A. Volkamer in Annual Reports in Medicinal Chemistry, Vol. 50 (Ed.: R. A. Goodnow), Academic Press, Cambridge, 2017, pp. 197-236.
M. W. Karaman, S. Herrgard, D. K. Treiber, P. Gallant, C. E. Atteridge, B. T. Campbell, K. W. Chan, P. Ciceri, M. I. Davis, P. T. Edeen, R. Faraoni, M. Floyd, J. P. Hunt, D. J. Lockhart, Z. V. Milanov, M. J. Morrison, G. Pallares, H. K. Patel, S. Pritchard, L. M. Wodicka, P. P. Zarrinkar, Nat. Biotechnol. 2008, 26, 127.
E. D. G. Fleuren, L. Zhang, J. Wu, R. J. Daly, Nat. Rev. Cancer 2016, 16, 83;
A. Di Cristofano, in Current Topics in Developmental Biology, Vol. 123 (Ed.: A. Jenny), Academic Press, Cambridge, 2017, pp. 49-71;
R. Basnet, G. Q. Gong, C. Li, M.-W. Wang, Acta Pharm. Sin. B 2018, 8, 767-771;
N. Maltsev, A. Rzhetsky, T. C. Gilliam, Systems Analysis of Human Multigene Disorders, Springer, New York, 2014.
M. Hammond, D. G. Washburn, T. H. Hoang, S. Manns, J. S. Frazee, H. Nakamura, J. R. Patterson, W. Trizna, C. Wu, L. M. Azzarano, R. Nagilla, M. Nord, R. Trejo, M. S. Head, B. Zhao, A. M. Smallwood, K. Hightower, N. J. Laping, C. G. Schnackenberg, S. K. Thompson, Bioorg. Med. Chem. Lett. 2009, 19, 4441-4445;
N. Halland, F. Schmidt, T. Weiss, J. Saas, Z. Li, J. Czech, M. Dreyer, A. Hofmeister, K. Mertsch, U. Dietz, C. Strübing, M. Nazare, ACS Med. Chem. Lett. 2015, 6, 73-78;
T. F. Ackermann, K. M. Boini, N. Beier, W. Scholz, T. Fuchss, F. Lang, Cell. Physiol. Biochem. 2011, 28, 137-146;
G. Q. Gong, K. Wang, X.-C. Dai, Y. Zhou, R. Basnet, Y. Chen, D.-H. Yang, W.-J. Lee, C. M. Buchanan, J. U. Flanagan, P. R. Shepherd, Y. Chen, M.-W. Wang, Acta Pharmacol. Sin. 2018, 39, 1902-1912;
F. Ortuso, R. Amato, A. Artese, L. D′antona, G. Costa, C. Talarico, F. Gigliotti, C. Bianco, F. Trapasso, S. Schenone, F. Musumeci, L. Botta, N. Perrotti, S. Alcaro, J. Chem. Inf. Model. 2014, 54, 1828-1832;
L. D′Antona, R. Amato, C. Talarico, F. Ortuso, M. Menniti, V. Dattilo, R. Iuliano, F. Gigliotti, A. Artese, G. Costa, S. Schenone, F. Musumeci, C. Abbruzzese, L. Botta, F. Trapasso, S. Alcaro, M. G. Paggi, N. Perrotti, Cell. Physiol. Biochem. 2015, 25, 2006-2018.
M. E. Welsch, S. A. Snyder, B. R. Stockwell, Curr. Opin. Chem. Biol. 2010, 14, 347-361;
S. R. Langdon, N. Brown, J. Blagg, J. Chem. Inf. Model. 2011, 51, 2174-2185;
E. J. Barreiro, in Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis Evaluation, The Royal Society of Chemistry, London, 2016, pp. 1-15.
J. Schoene, H. Bel Abed, P. Schmieder, M. Christmann, M. Nazaré, Chem. Eur. J. 2018, 24, 9090-9100.
R. Chun, S. Kim, S. H. Han, S. Han, S. H. Lee, N. K. Mishra, Y. H. Jung, H. S. Kim, I. S. Kim, Adv. Synth. Catal. 2019, 361, 1617-1626;
J. Schoene, H. Bel Abed, M. Christmann, M. Nazaré, Tetrahedron Lett. 2017, 58, 1633-1635;
H. Bel Abed, J. Schoene, M. Christmann, M. Nazaré, Org. Biomol. Chem. 2016, 14, 8520-8528;
P. Jones, S. Altamura, J. Boueres, F. Ferrigno, M. Fonsi, C. Giomini, S. Lamartina, E. Monteagudo, J. M. Ontoria, M. V. Orsale, M. C. Palumbi, S. Pesci, G. Roscilli, R. Scarpelli, C. Schultz-Fademrecht, C. Toniatti, M. Rowley, J. Med. Chem. 2009, 52, 7170-7185;
S. Gupta, P. E. Spiess, Ther. Adv. Urol. 2013, 5, 223-232;
M. De Angelis, F. Stossi, K. A. Carlson, B. S. Katzenellenbogen, J. A. Katzenellenbogen, J. Med. Chem. 2005, 48, 1132-1144;
S. M. Moore, A. J. Khalaj, S. Kumar, Z. Winchester, J. Yoon, T. Yoo, L. Martinez-Torres, N. Yasui, J. A. Katzenellenbogen, S. K. Tiwari-Woodruff, Proc. Natl. Acad. Sci. USA 2014, 111, 18061-18066;
J. A. Pfefferkorn, M. Tu, K. J. Filipski, A. Guzman-Perez, J. Bian, G. E. Aspnes, M. F. Sammons, W. Song, J.-C. Li, C. S. Jones, L. Patel, T. Rasmusson, D. Zeng, K. Karki, M. Hamilton, R. Hank, K. Atkinson, J. Litchfield, R. Aiello, L. Baker, N. Barucci, P. Bourassa, F. Bourbounais, T. D′Aquila, D. R. Derksen, M. MacDougall, A. Robertson, Bioorg. Med. Chem. Lett. 2012, 22, 7100-7105;
“3-Aminoindazole or 3-Amino-4,5,6,7-Tetrahydroindazole Derivatives”, G. M. Benson, K. Bleicher, S. Feng, U. Grether, B. Kuhn, R. E. Martin, J.-M. Plancher, H. Richter, R. Markus, S. Taylor (F. Hoffmann-La Roche AG), Int. PCT Pub. No. WO2010034657 A1, 2010;
“Viral Polymerase Inhibitors”, R. Halim, M. Harding, R. Hufton, C. J. Morton, S. Jahangiri, B. R. Pool, T. P. Jeynes, A. G. Draffan, M. J. Lilly, B. Frey (Biota Scientific Management Pty. Ltd.), Int. PCT Pub. No. WO2012051659, 2012;
J. S. Zhu, C. J. Li, K. Y. Tsui, N. Kraemer, J.-H. Son, M. J. Haddadin, D. J. Tantillo, M. J. Kurth, J. Am. Chem. Soc. 2019, 141, 6247-6253.
“N-(4-(Azaindazol-6-yl)phenyl)sulfonamides and Their Use as Pharmaceuticals”, M. Nazaré, N. Halland, F. Schmidt, H.-W. Kleemann, T. Weiss, J. Saas, C. Struebing (Sanofi), Int. PCT Pub. No. WO2014140065, 2014;
“N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)phenyl]sulfonamides and Their Use as Pharmaceuticals”, M. Nazaré, N. Halland, F. Schmidt, T. Weiss, U. Dietz, A. Hofmeister, J.-C. Carry (Sanofi), Int. PCT Pub. No. WO2013041119, 2013;
N. Halland, M. Nazaré, O. R′Kyek, J. Alonso, M. Urmann, A. Lindenschmidt, Angew. Chem. Int. Ed. 2009, 48, 6879-6882;
Angew. Chem. 2009, 121, 7011-7014.
A. J. Kooistra, G. K. Kanev, O. P. J. van Linden, R. Leurs, I. J. P. de Esch, C. de Graaf, Nucleic Acids Res. 2016, 44, D365-D371;
A. P. Bento, A. Gaulton, A. Hersey, L. J. Bellis, J. Chambers, M. Davies, F. A. Krüger, Y. Light, L. Mak, S. McGlinchey, M. Nowotka, G. Papadatos, R. Santos, J. P. Overington, Nucleic Acids Res. 2014, 42, D1083-D1090.
T. V. Nykaza, T. S. Harrison, A. Ghosh, R. A. Putnik, A. T. Radosevich, J. Am. Chem. Soc. 2017, 139, 6839-6842;
N. E. Genung, L. Wei, G. E. Aspnes, Org. Lett. 2014, 16, 3114-3117;
J. Cadogan, Q. Rev. Chem. Soc. 1968, 22, 222-251.
D. Gfeller, A. Grosdidier, M. Wirth, A. Daina, O. Michielin, V. Zoete, Nucleic Acids Res. 2014, 42, W32-W38; URL: http://www.swisstargetprediction.ch/.
P. Castel, H. Ellis, R. Bago, E. Toska, P. Razavi, F. J. Carmona, S. Kannan, C. S. Verma, M. Dickler, S. Chandarlapaty, E. Brogi, D. R. Alessi, J. Baselga, M. Scaltriti, Cancer Cell 2016, 30, 229-242;
R. Bago, E. Sommer, P. Castel, C. Crafter, F. P. Bailey, N. Shpiro, J. Baselga, D. Cross, P. A. Eyers, D. R. Alessi, EMBO J. 2016, 35, 1902-1922.
S. Eid, S. Turk, A. Volkamer, F. Rippmann, S. Fulle BMC Bioinformatics 2017, 18, 16.