Substituent Effects on Drug-Receptor H-bond Interactions: Correlations Useful for the Design of Kinase Inhibitors

Journal of Medicinal Chemistry

Volumn 59, Issue 23, 2016, Pages 10629-10641

  Lawhorn, Brian G ^a   Philp, Joanne ^a   Graves, Alan P ^a   Holt, Dennis A ^a   Gatto, Gregory J ^a   Kallander, Lara S ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [(7H PYRROLO[2,3 D]PYRIMIDIN 4 YL)AMINO] 4 (ETHYLAMINO) N METHYLBENZENESULFONAMIDE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] 4 PYRIMIDINYL]AMINO] 4 FLUORO N METHYLBENZENESULFONAMIDE TRIFLUOROACETATE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] 4 PYRIMIDINYL]AMINO]N METHYL[(TRIFLUOROMETHYL)OXY]BENZENESULFONAMIDE TRIFLUOROACETATE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N METHYL 4 (ETHYLAMINO)BENZENESULFONAMIDE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N METHYL 4 (METHYLAMINO)BENZENESULFONAMIDE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N METHYL 4 (METHYLTHIO)BENZENESULFONAMIDE TRIFLUOROACETATE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N METHYL 4 (PROPYLAMINO)BENZENESULFONAMIDE; 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N,4 DIMETHYLBENZENESULFONAMIDE TRIFLUOROACETATE; 3 [[6 [(4 CHLOROPHENYL)AMINO]PYRIMIDIN 4 YL]AMINO] N METHYLBENZENESULFONAMIDE; 3 [[6,7 BIS(METHYLOXY) 4 QUINAZOLINYL]AMINO] N METHYLBENZENESULFONAMIDE; 4 ( THYLOXY) N METHYL 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO)BENZENESULFONAMIDE; 4 AMINO 3 [[6 [(4 CHLOROPHENYLAMINO] 4 PYRIMIDINYL]AMINO N METHYLBENZENESULFONAMIDE TRIFLUOROACETATE; 4 CHLORO 3 [[6 [(4 CHLOROPHENYL)AMINO] 4 PYRIMIDINYL]AMINO] N METHYLBENZENESULFONAMIDE TRIFLUOROACETATE; 4-HYDROXY N METHYL 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO)BENZENESULFONAMIDE TRIFLUOROACETATE; ADENOSINE TRIPHOSPHATE; B RAF KINASE; HYDROGEN; N METHYL 2 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YL AMINO) 4 BIPHENYLSULFONAMIDE TRIFLUOROACETATE; N METHYL 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO) 4 [(TRIFLUOROMETHYL)OXY]BENZENESULFONAMIDE; N METHYL 4 (METHYLOXY) 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO)BENZENESULFONAMIDE; N METHYL 4 (METHYLTHIO) 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO)BENZENESULFONAMIDE; N METHYL 4 (PROPYLAMINO) 3 (1H PYRROLO[2,3 D]PYRIMIDIN 4 YLAMINO)BENZENESULFONAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NITROGEN; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN TYROSINE KINASE; QUINAZOLINE; SULFONAMIDE; TROPONIN I INTERACTING PROTEIN KINASE; UNCLASSIFIED DRUG; UNINDEXED DRUG; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; PROTEIN KINASE INHIBITOR; TNNI3K PROTEIN, HUMAN;

ARTICLE; DRUG PROTEIN BINDING; HINGE REGION; HYDROGEN BOND; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DESIGN; HUMAN;

DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; HYDROGEN BONDING; MAP KINASE KINASE KINASES; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85003598117     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01342     Document Type: Article

References (46)

1. Lal, H.; Ahmad, F.; Parikh, S.; Force, T. Troponin I-interacting protein kinase: a novel cardiac-specific kinase, emerging as a molecular target for the treatment of cardiac disease Circ. J. 2014, 78, 1514-1519 10.1253/circj.CJ-14-0543
2. Abraham, D. M.; Marchuk, D. A. Inhibition of the cardiomyocyte-specific troponin I-interacting kinase limits oxidative stress, injury, and adverse remodeling due to ischemic heart disease Circ. Res. 2014, 114, 938-940 10.1161/CIRCRESAHA.113.303238
3. Tang, H.; Xiao, K.; Mao, L.; Rockman, H. A.; Marchuk, D. A. Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction J. Mol. Cell. Cardiol. 2013, 54, 101-111 10.1016/j.yjmcc.2012.10.004
4. Wheeler, F. C.; Tang, H.; Marks, O. A.; Hadnott, T. N.; Chu, P. L.; Mao, L.; Rockman, H. A.; Marchuk, D. A. Tnni3k modifies disease progression in murine models of cardiomyopathy PLoS Genet. 2009, 5, e1000647 10.1371/journal.pgen.1000647
5. Vagnozzi, R. J.; Gatto, G. J., Jr.; Kallander, L. S.; Hoffman, N. E.; Mallilankaraman, K.; Ballard, V. L. T.; Lawhorn, B. G.; Stoy, P.; Philp, J.; Graves, A. P.; Naito, Y.; Lepore, J. J.; Gao, E.; Madesh, M.; Force, T. Inhibition of the cardiomyocyte-specific TNNI3K limits oxidative stress, injury, and adverse remodeling in the ischemic heart Sci. Transl. Med. 2013, 5, 207ra141 10.1126/scitranslmed.3006479
6. Lawhorn, B. G.; Philp, J.; Zhao, S.; Louer, C.; Hammond, M.; Cheung, M.; Fries, H.; Graves, A. P.; Shewchuk, L.; Wang, L.; Cottom, J. E.; Qi, H.; Zhao, H.; Totoritis, R.; Zhang, G.; Schwartz, B.; Li, H.; Sweitzer, S.; Holt, D. A.; Gatto, G. J., Jr.; Kallander, L. S. Identification of purines and 7-deazapurines as potent and selective type I inhibitors of troponin I-interacting kinase (TNNI3K) J. Med. Chem. 2015, 58, 7431-7448 10.1021/acs.jmedchem.5b00931
7. Lawhorn, B. G.; Philp, J.; Graves, A. P.; Shewchuk, L.; Holt, D. A.; Gatto, G. J., Jr.; Kallander, L. S. GSK114: A selective inhibitor for identifying the biological role of TNNI3K Bioorg. Med. Chem. Lett. 2016, 26, 3355-3358 10.1016/j.bmcl.2016.05.033
8. Soman, G.; Narayanan, J.; Martin, B. L.; Graves, D. J. Use of substituted (benzylidineamino)guanidines in the study of guanidino group specific ADP-ribosyltransferase Biochemistry 1986, 25, 4113-4119 10.1021/bi00362a019
9. Gebler, J. C.; Woodside, A. B.; Poulter, C. D. Dimethylallyltryptophan synthase. An enzyme-catalyzed electrophilic aromatic substitution J. Am. Chem. Soc. 1992, 114, 7354-7360 10.1021/ja00045a004
10. Abramovitz, A. S.; Massey, V. Interaction of phenols with old yellow enzyme J. Biol. Chem. 1976, 251, 5327-5336
11. Romero, F. A.; Hwang, I.; Boger, D. L. Delineation of a fundamental α-ketoheterocycle substituent effect for use in the design of enzyme inhibitors J. Am. Chem. Soc. 2006, 128, 14004-14005 10.1021/ja064522b
12. Hansch, C.; Leo, A.; Taft, R. W. A survey of Hamett substituent constants and resonance and field parameters Chem. Rev. 1991, 91, 165-195 10.1021/cr00002a004
13. Gennari, C.; Gude, M.; Potenza, D.; Piarulli, U. Hydrogen-bonding donor/acceptor scales in β-sulfonamidopeptides Chem.-Eur. J. 1998, 4, 1924-1931 10.1002/(SICI)1521-3765(19981002)4:10<1924::AID-CHEM1924>3.0.CO;2-P
14. BHX database: Toward a better understanding of hydrogen-bond basicity for medicinal chemists J. Med. Chem. 2009, 52, 4073-4086 10.1021/jm801331y
15. Abraham, M. H.; Duce, P. P.; Prior, D. V.; Barratt, D. G.; Morris, J. J.; Taylor, P. J. Hydrogen bonding. Part 9. Solute proton donor and proton acceptor scales for use in drug design J. Chem. Soc., Perkin Trans. 2 1989, 1355-1375 10.1039/p29890001355
16. Gomes, J. R. B.; Gomes, P. Gas-phase acidity of sulfonamides: implications for reactivity and prodrug design Tetrahedron 2005, 61, 2705-2712 10.1016/j.tet.2005.01.034
17. Nyasse, B.; Grehn, L.; Ragnarsson, U.; Maia, H. L. S.; Monteiro, L. S.; Leito, I.; Koppel, I.; Koppel, J. Synthesis and cathodic cleavage of a set of substituted benzene-sulfonamides including the corresponding tert-butyl sulfonyl-carbamates: pKa of sulfonamides J. Chem. Soc., Perkin Trans. 1 1995, 2025-2031 10.1039/p19950002025
18. Ahlbrecht, H.; Duber, E. O.; Epsztajn, J.; Marcinkowski, R. M. K. Delocalisation, conformation and basicity of anilines Tetrahedron 1984, 40, 1157-1165 10.1016/S0040-4020(01)99321-4
19. Zhang, J.; Yang, P. L.; Gray, N. S. Targeting cancer with small molecule kinase inhibitors Nat. Rev. Cancer 2009, 9, 28-39 10.1038/nrc2559
20. Ghose, A. K.; Herbertz, T.; Pippin, D. A.; Salvino, J. M.; Mallamo, J. P. Knowledge based prediction of ligand binding modes and rational inhibitor design for kinase drug discovery J. Med. Chem. 2008, 51, 5149-5171 10.1021/jm800475y
21. Rewcastle, G. W.; Denny, W. A.; Bridges, A. J.; Zhou, H.; Cody, D. R.; McMichael, A.; Fry, D. W. Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]-and 4-(phenylamino)quinazolines as potent adenosine-5′-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor J. Med. Chem. 1995, 38, 3482-3487 10.1021/jm00018a008
22. Maguire, M. P.; Sheets, K. R.; McVety, K.; Spada, A. P.; Zilberstein, A. A new series of PDGF receptor tyrosine kinase inhibitors: 3-substituted quinoline derivatives J. Med. Chem. 1994, 37, 2129-2137 10.1021/jm00040a003
23. Dolle, R. E.; Dunn, J. A.; Bobko, M.; Singh, B.; Kuster, J. E.; Baizman, E.; Harris, A. L.; Sawutz, D. G.; Miller, D.; Wang, S.; Faltynek, C. R.; Xie, W.; Sarup, J.; Bode, C.; Pagani, E. D.; Silver, P. J. 5,7-dimethoxy-3-(4-pyridinyl)quinoline is a potent and selective inhibitor of human vascular β-type platelet-derived growth factor receptor tyrosine kinase J. Med. Chem. 1994, 37, 2627-2629 10.1021/jm00043a002
24. Hennequin, L. F.; Thomas, A. P.; Johnstone, C.; Stokes, E. S. E.; Ple, P. A.; Lohmann, J.-J. M.; Ogilvie, D. J.; Dukes, M.; Wedge, S. R.; Curwen, J. O.; Kendrew, J.; Lambert-van der Brempt, C. Design and structure-activity relationships of a new class of potent VEGF receptor tyrosine kinase inhibitors J. Med. Chem. 1999, 42, 5369-5389 10.1021/jm990345w
25. Potashman, M. H.; Bready, J.; Coxon, A.; DeMelfi, T. M., Jr.; DiPietro, L.; Doerr, N.; Elbaum, D.; Estrada, J.; Gallant, P.; Germain, J.; Gu, Y.; Harmange, J.-C.; Kaufman, S. A.; Kendall, R.; Kim, J. L.; Kumar, G. N.; Long, A. M.; Neervannan, S.; Patel, V. F.; Polverino, A.; Rose, P.; van der Plas, S.; Whittington, D.; Zanon, R.; Zhao, H. Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors J. Med. Chem. 2007, 50, 4351-4373 10.1021/jm070034i
26. Pierce, A. C.; Sandretto, K. L.; Bemis, G. W. Kinase inhibitors and the case for CH-O hydrogen bonds in protein-ligand binding Proteins: Struct., Funct., Genet. 2002, 49, 567-576 10.1002/prot.10259
27. Bissantz, C.; Kuhn, B.; Stahl, M. A medicinal chemist’s guide to molecular interactions J. Med. Chem. 2010, 53, 5061-5084 10.1021/jm100112j
28. King, A. J.; Patrick, D. R.; Batorsky, R. S.; Ho, M. L.; Do, H. T.; Zhang, S. Y.; Kumar, R.; Rusnak, D. W.; Takle, A. K.; Wilson, D. W.; Hugger, E.; Wang, L.; Karreth, F.; Lougheed, J. C.; Lee, J.; Chau, D.; Stout, T. J.; May, E. W.; Rominger, C. M.; Schaber, M. D.; Luo, L.; Lakdawala, A. S.; Adams, J. L.; Contractor, R. G.; Smalley, K. S. M.; Herlyn, M.; Morrissey, M. M.; Tuveson, D. A.; Huang, P. S. Demonstrations of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinse inhibitor SB-590885 Cancer Res. 2006, 66, 11100-11105 10.1158/0008-5472.CAN-06-2554
29. Cozzi, F.; Siegel, J. S. Interaction between stacked aryl groups in 1,8-diarylnapthalenes: dominance of polar/π over charge-transfer effects Pure Appl. Chem. 1995, 67, 683-689 10.1351/pac199567050683
30. Cozzi, F.; Cinquini, M.; Annunziata, R.; Dwyer, T.; Siegel, J. S. Polar/π interactions between stacked aryls in 1,8-diarylnapthalenes J. Am. Chem. Soc. 1992, 114, 5729-5733 10.1021/ja00040a036
31. Rashkin, M. J.; Waters, M. L. Unexpected substituent effects in offset π-π stacked interactions in water J. Am. Chem. Soc. 2002, 124, 1860-1861 10.1021/ja016508z
32. Meyer, E. A.; Castellano, R. K.; Diederich, F. Interactions with aromatic rings in chemical and biological recognition Angew. Chem., Int. Ed. 2003, 42, 1210-1250 10.1002/anie.200390319
33. Huggins, D. J.; Sherman, W.; Tidor, B. Rational approaches to improving selectivity in drug design J. Med. Chem. 2012, 55, 1424-1444 10.1021/jm2010332
34. Platts, J. A. Theoretical prediction of hydrogen bond basicity Phys. Chem. Chem. Phys. 2000, 2, 3115-3120 10.1039/b003026k
35. Zhang, Q.; Liu, Y.; Gao, F.; Ding, Q.; Cho, C.; Hur, W.; Jin, Y.; Uno, T.; Joazeiro, C. A. P.; Gray, N. Discovery of EGFR selective 4,6-disubstituted pyrimidines from a combinatorial kinase-directed heterocycle library J. Am. Chem. Soc. 2006, 128, 2182-2183 10.1021/ja0567485
36. Zhang, G.; Ren, P.; Gray, N. S.; Sim, T.; Liu, Y.; Wang, X.; Che, J.; Tian, S.-S.; Sandberg, M. L.; Spalding, T. A.; Romeo, R.; Iskandar, M.; Chow, D.; Seidel, H. M.; Karanewsky, D. S.; He, Y. Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part 1 Bioorg. Med. Chem. Lett. 2008, 18, 5618-5621 10.1016/j.bmcl.2008.08.104
37. Deng, X.; Okram, B.; Ding, Q.; Zhang, J.; Choi, Y.; Adrian, F. J.; Wojciechowski, A.; Zhang, G.; Che, J.; Bursulaya, B.; Cowan-Jacob, S. W.; Rummel, G.; Sim, T.; Gray, N. S. Expanding the diversity of allosteric Bcr-Abl inhibitors J. Med. Chem. 2010, 53, 6934-6946 10.1021/jm100555f
38. Morris, J. J.; Hughes, L. R.; Glen, A. T.; Taylor, P. J. Non-steroidal antiandrogens. Design of novel compounds based on an infrared study of the dominant conformation and hydrogen-bonding properties of a series of anilide antiandrogens J. Med. Chem. 1991, 34, 447-455 10.1021/jm00105a067
39. Bingham, A. H.; Davenport, R. J.; Gowers, L.; Knight, R. L.; Lowe, C.; Owen, D. A.; Parry, D. M.; Pitt, W. R. A novel series of potent and selective IKK2 inhibitors Bioorg. Med. Chem. Lett. 2004, 14, 409-412 10.1016/j.bmcl.2003.10.047
40. For a recent publication discussing the concept of modulating binding affinity through protein-ligand hydrogen bonding, see Chen, D.; Oezguen, N.; Urvil, P.; Ferguson, C.; Dann, S. M.; Savidge, T. C. Regulation of protein-ligand binding affinity by hydrogen bond pairing Sci. Adv. 2016, 2, e1501240 10.1126/sciadv.1501240
41. Hammond, M.; Kallander, L. S.; Lawhorn, B. G.; Philp, J.; Sarpong, M. A.; Seefeld, M. A. Azolopyrimidine compounds as kinase inhibitors and their preparations and use in the treatment of diseases and methods. PCT Int. Appl. WO2011149827, 2011.
42. Kallander, L. S.; Lawhorn, B. G.; Philp, J. U. S. Patent 8,859,571 B2, 2014.
43. Kallander, L. S.; Lawhorn, B. G.; Philp, J.; Zhao, Y. PCT Int. Appl. WO2011088027, 2011.
44. Kallander, L. S.; Philp, J. PCT Int. Appl. WO2011088031, 2011.
45. Hammond, M.; Zhao, Y. PCT Int. Appl. WO2011056739, 2011.
46. Bochevarov, A. D.; Harder, E.; Hughes, T. F.; Greenwood, J. R.; Braden, D. A.; Philipp, D. M.; Rinaldo, D.; Halls, M. D.; Zhang, J.; Friesner, R. A. Jaguar: A high-performance quantum chemistry software program with strenghts in life and materials sciences Int. J. Quantum Chem. 2013, 113, 2110-2142 10.1002/qua.24481