Determinants of activity at human toll-like receptors 7 and 8: Quantitative Structure-Activity Relationship (QSAR) of diverse heterocyclic scaffolds

Journal of Medicinal Chemistry

Volumn 57, Issue 19, 2014, Pages 7955-7970

  Yoo, Euna ^a   Salunke, Deepak B ^a   Sil, Diptesh ^a   Guo, Xiaoqiang ^a   Salyer, Alex C D ^a   Hermanson, Alec R ^a   Kumar, Manoj ^a   Malladi, Subbalakshmi S ^a   Balakrishna, Rajalakshmi ^a   Thompson, Ward H ^a   Tanji, Hiromi ^b   Ohto, Umeharu ^b   Shimizu, Toshiyuki ^b   David, Sunil A ^a  

^a UNIVERSITY OF KANSAS   (United States)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2 (PROPYLAMINO)OXAZOLO[4,5 C]QUINOLINE 5 OXIDE; 2 BUTYL 2,3 DIHYDROIMIDAZO[1,2 C]QUINAZOLIN 5 AMINE; 2 BUTYL 5 CHLORO[1,2,4]TRIAZOLO[1,5 C]QUINAZOLINE; 2 BUTYLIMIDAZO[1,2 C]QUINAZOLIN 5 AMINE; 2 BUTYLOXAZOLO[4,5 C]QUINOLIN 4 AMINE; 2 BUTYLOXAZOLO[4,5 C]QUINOLINE; 2 BUTYLOXAZOLO[4,5 C]QUINOLINE 5 OXIDE; 2 BUTYLOXAZOLO[5,4 C]QUINOLIN 4 AMINE; 2 BUTYLOXAZOLO[5,4 C]QUINOLINE; 2 BUTYLOXAZOLO[5,4 C]QUINOLINE 5 OXIDE; 2 BUTYLTHIAZOLO[4,5 C]QUINOLINE; 2 BUTYLTHIAZOLO[5,4 C]QUINOLIN 4 AMINE; 2 BUTYLTHIAZOLO[5,4 C]QUINOLINE; 2 BUTYLTHIAZOLO[5,4 C]QUINOLINE 5 OXIDE; 2 BUTYL[1,2,4]TRIAZOLO[1,5 C]QUINAZOLIN 5(6H) ONE; 2 PROPIONAMIDOTHIAZOLO[4,5 C]QUINOLINE 5 OXIDE; 2 [(2 CHLOROQUINAZOLIN 4 YL)AMINO]HEXAN 1 OL; HETEROCYCLIC COMPOUND; METHYL (2 CYANOPHENYL)CARBAMATE; N (3 BROMOQUINOLIN 4 YL)VALERAMIDE; N (QUINOLIN 4 YL)VALERAMIDE; N 4 AMINOTHIAZOLO[4,5 C]QUINOLIN 2 YL)PROPIONAMIDE; N PROPYLOXAZOLO[4,5 C]QUINOLIN 2 AMINE; N PROPYLTHIAZOLO[4,5 C]QUINOLIN 2 AMINE; N2 PROPYLOXAZOLO[4,5 C]QUINOLINE 2 4 DIAMINE; N2 PROPYLTHIAZOLO[4,5 C]QUINOLIN 2 4 DIAMINE; QUINAZOLINE 2,4(1H,3H) DIONE; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; UNCLASSIFIED DRUG; UNINDEXED DRUG; CHEMOKINE; CYTOKINE; TLR7 PROTEIN, HUMAN; TLR8 PROTEIN, HUMAN;

ARTICLE; BIOLOGICAL ACTIVITY; BLOOD; CARBON NUCLEAR MAGNETIC RESONANCE; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DENSITY FUNCTIONAL THEORY; DIPOLE; EX VIVO STUDY; HUMAN; HUMAN CELL; HYDROGEN BOND; MICROWAVE IRRADIATION; MONONUCLEAR CELL; PROTON NUCLEAR MAGNETIC RESONANCE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STATIC ELECTRICITY; THIN LAYER CHROMATOGRAPHY; AGONISTS; BIOSYNTHESIS; CHEMISTRY; PHYSIOLOGY;

CHEMOKINES; CYTOKINES; HETEROCYCLIC COMPOUNDS; HUMANS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; TOLL-LIKE RECEPTOR 7; TOLL-LIKE RECEPTOR 8;

EID: 84907889492     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500744f     Document Type: Article

References (47)

1. Iwasaki, A.; Medzhitov, R. Toll-like receptor control of the adaptive immune responses Nat. Immunol. 2004, 5, 987-995
2. Kawai, T.; Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors Nat. Immunol. 2010, 11, 373-384
3. Janeway, C. A., Jr.; Medzhitov, R. Innate immune recognition Annu. Rev. Immunol. 2002, 20, 197-216
4. Akira, S.; Takeda, K.; Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity Nat. Immunol. 2001, 2, 675-680
5. Kumagai, Y.; Takeuchi, O.; Akira, S. Pathogen recognition by innate receptors J. Infect. Chemother. 2008, 14, 86-92
6. Takeda, K.; Akira, S. Toll-like receptors. Curr. Protoc. Immunol. 2007, DOI: 10.1002/0471142735.im1412s77.
7. Yu, L.; Wang, L.; Chen, S. Endogenous Toll-like receptor ligands and their biological significance J. Cell. Mol. Med. 2010, 14, 2592-2603
8. Spyvee, M.; Hawkins, L. D.; Ishizaka, S. T. Modulators of Toll- like receptor (TLR) signaling Annu. Rep. Med. Chem. 2010, 45, 191-207
9. ONeill, L. A.; Golenbock, D.; Bowie, A. G. The history of Toll-like receptors-redefining innate immunity Nat. Rev. Immunol. 2013, 13, 453-460
10. Meyer, T.; Stockfleth, E. Clinical investigations of Toll-like receptor agonists Expert Opin. Invest. Drugs 2008, 17, 1051-1065
11. Kimbrell, M. R.; Warshakoon, H.; Cromer, J. R.; Malladi, S.; Hood, J. D.; Balakrishna, R.; Scholdberg, T. A.; David, S. A. Comparison of the immunostimulatory and proinflammatory activities of candidate Gram-positive endotoxins, lipoteichoic acid, peptidoglycan, and lipopeptides, in murine and human cells Immunol. Lett. 2008, 118, 132-141
12. Warshakoon, H. J.; Hood, J. D.; Kimbrell, M. R.; Malladi, S.; Wu, W. Y.; Shukla, N. M.; Agnihotri, G.; Sil, D.; David, S. A. Potential adjuvantic properties of innate immune stimuli Hum. Vaccines 2009, 5, 381-394
13. Agnihotri, G.; Ukani, R.; Malladi, S. S.; Warshakoon, H. J.; Balakrishna, R.; Wang, X.; David, S. A. Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic gammaglutamyldiaminopimelic acid derivatives J. Med. Chem. 2011, 54, 1490-1510
14. Wu, W.; Li, R.; Malladi, S. S.; Warshakoon, H. J.; Kimbrell, M. R.; Amolins, M. W.; Ukani, R.; Datta, A.; David, S. A. Structure-activity relationships in Toll-like receptor-2 agonistic diacylthioglycerol lipopeptides J. Med. Chem. 2010, 53, 3198-3213
15. Agnihotri, G.; Crall, B. M.; Lewis, T. C.; Day, T. P.; Balakrishna, R.; Warshakoon, H. J.; Malladi, S. S.; David, S. A. Structure-activity relationships in Toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides J. Med. Chem. 2011, 54, 8148-8160
16. Salunke, D. B.; Shukla, N. M.; Yoo, E.; Crall, B. M.; Balakrishna, R.; Malladi, S. S.; David, S. A. Structure-activity relationships in human Toll-like receptor 2-specific monoacyl lipopeptides J. Med. Chem. 2012, 55, 3353-3363
17. Salunke, D. B.; Connelly, S. W.; Shukla, N. M.; Hermanson, A. R.; Fox, L. M.; David, S. A. Design and development of stable, water-soluble, human Toll-like receptor 2 specific monoacyl lipopeptides as candidate vaccine adjuvants J. Med. Chem. 2013, 56, 5885-5900
18. Ukani, R.; Lewis, T. C.; Day, T. P.; Wu, W.; Malladi, S. S.; Warshakoon, H. J.; David, S. A. Potent adjuvantic activity of a CCR1-agonistic bis-quinoline Bioorg. Med. Chem. Lett. 2012, 22, 293-295
19. Vasilakos, J. P.; Tomai, M. A. The use of Toll-like receptor 7/8 agonists as vaccine adjuvants Expert Rev. Vaccines 2013, 12, 809-819
20. Akira, S.; Takeda, K. Toll-like receptor signaling Nat. Rev. Immunol. 2004, 4, 499-511
21. Shukla, N. M.; Kimbrell, M. R.; Malladi, S. S.; David, S. A. Regioisomerism-dependent TLR7 agonism and antagonism in an imidazoquinoline Bioorg. Med. Chem. Lett. 2009, 19, 2211-2214
22. Shukla, N. M.; Malladi, S. S.; Mutz, C. A.; Balakrishna, R.; David, S. A. Structure-activity relationships in human Toll-like receptor 7-active imidazoquinoline analogues J. Med. Chem. 2010, 53, 4450-4465
23. Yoo, E.; Crall, B. M.; Balakrishna, R.; Malladi, S. S.; Fox, L. M.; Hermanson, A. R.; David, S. A. Structure-activity relationships in Toll- like receptor 7 agonistic 1 H -imidazo[4,5- c ]pyridines Org. Biomol. Chem. 2013, 11, 6526-6545
24. Kokatla, H. P.; Yoo, E.; Salunke, D. B.; Sil, D.; Ng, C. F.; Balakrishna, R.; Malladi, S. S.; Fox, L. M.; David, S. A. Toll-like receptor-8 agonistic activities in C2, C4, and C8 modified thiazolo[4,5- c ]quinolines Org. Biomol. Chem. 2013, 11, 1179-1198
25. Salunke, D. B.; Yoo, E.; Shukla, N. M.; Balakrishna, R.; Malladi, S. S.; Serafin, K. J.; Day, V. W.; Wang, X.; David, S. A. Structure-activity relationships in human Toll-like receptor 8-active 2,3-diamino-furo[2,3- c ]pyridines J. Med. Chem. 2012, 55, 8137-8151
26. Kokatla, H. P.; Sil, D.; Malladi, S. S.; Balakrishna, R.; Hermanson, A. R.; Fox, L. M.; Wang, X.; Dixit, A.; David, S. A. Exquisite selectivity for human Toll-like receptor 8 in substituted furo[2,3- c ]quinolines J. Med. Chem. 2013, 56, 6871-6885
27. Tanji, H.; Ohto, U.; Shibata, T.; Miyake, K.; Shimizu, T. Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands Science 2013, 339, 1426-1429
28. Kokatla, H. P.; Sil, D.; Tanji, H.; Ohto, U.; Malladi, S. S.; Fox, L. M.; Shimizu, T.; David, S. A. Structure-based design of novel human Toll-like receptor 8 agonists ChemMedChem 2014, 9, 719-723
29. Boehm, H. J.; Flohr, A.; Stahl, M. Scaffold hopping Drug Discovery Today: Technol. 2004, 1, 217-224
30. Lloyd, D. G.; Buenemann, C. L.; Todorov, N. P.; Manallack, D. T.; Dean, P. M. Scaffold hopping in de novo design. Ligand generation in the absence of receptor information J. Med. Chem. 2004, 47, 493-496
31. Sun, H.; Tawa, G.; Wallqvist, A. Classification of scaffold hopping approaches Drug Discovery Today 2012, 17, 310-324
32. Murray, J. S.; Politzer, P. The use of molecular electrostatic potential in medicinal chemistry. Quantum Medicinal Chemistry; Wiley-VCH: New York, 2002; Vol. 17, pp 233-254.
33. Höltje, H.-D.; Höltje, M. Applications of quantum chemical methods in drug design. Quantum Medicinal Chemistry; Wiley-VCH: New York, 2002; Vol. 17, pp 255-274.
34. Lai, J. J.; Salunke, D. B.; Sun, C. M. Multistep microwave-assisted divergent synthesis of indolo-fused pyrazino-/diazepinoquinoxalinones on PEG support Org. Lett. 2010, 12, 2174-2177
35. Borchardt, A. J.; Beauregard, D.; Cook, T.; Davis, R. L.; Gamache, D. A.; Yanni, J. M. Heterocyclic inhibitors of histamine receptors for the treatment of disease. World Patent WO 2010/030785 A2, 2006.
36. Salio, M.; Speak, A. O.; Shepherd, D.; Polzella, P.; Illarionov, P. A.; Veerapen, N.; Besra, G. S.; Platt, F. M.; Cerundolo, V. Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 20490-20495
37. + T cells AIDS Res. Hum. Retroviruses 2001, 17, 59-63
38. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode Methods Enzymol. 1997, 276, 344-358
39. Vagin, A.; Teplyakov, A. Molecular replacement with MOLREP Acta Crystallogr. 2010, D66, 22-25
40. Battye, T. G.; Kontogiannis, L.; Johnson, O.; Powell, H. R.; Leslie, A. G. iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM Acta Crystallogr. 2011, D67, 271-281
41. Emsley, P.; Cowtan, K. Coot: model-building tools for molecular graphics Acta Crystallogr. 2004, D60, 2126-2132
42. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method Acta Crystallogr. 1997, D53, 240-255
43. Laskowski, R. A.; Macarthur, M. W.; Moss, D. S.; Thornton, J. M. Procheck-a program to check the stereochemical quality of protein structures J. Appl. Crystallogr. 1993, 26, 283-291
44. DeLano, W. L. The PyMOL Molecular Graphics System; DeLano Scientific LLC: Palo Alto, CA, U.S., 2008; http://www.pymol.org.
45. Valiev, M.; Bylaska, E. J.; Govind, N.; Kowalski, K.; Straatsma, K. P.; van Dam, H. J. J.; Wang, D.; Nieplocha, J.; Apra, E.; Windus, T. L.; de Jong, W. A. NWChem: a comprehensive and scalable open-source solution for large scale molecular simulations Comput. Phys. Commun. 2010, 181, 1477-1489
46. Zhao, Y.; Truhlar, D. G. Density functionals with broad applicability in chemistry Acc. Chem. Res. 2008, 41, 157-167
47. GaussView03; Gaussian Inc.: Pittsburgh, PA, 2003.