Development of β-amino alcohol derivatives that inhibit toll-like receptor 4 mediated inflammatory response as potential antiseptics

Journal of Medicinal Chemistry

Volumn 54, Issue 13, 2011, Pages 4659-4669

  Chavez, Sherry A ^a   Martinko, Alexander J ^a   Lau, Corinna ^b   Pham, Michael N ^a   Cheng, Kui ^a   Bevan, Douglas E ^a   Mollnes, Tom E ^b,c   Yin, Hang ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b NORDLAND HOSPITAL   (Norway)

^c UNIVERSITY OF TROMSØ   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 (ALLYLOXY)PHENOXY] 3 [[[3,5 DIMETHYL 1 (2 VINYLBENZYL) 1H PYRAZOL 4 YL]METHYL](METHYL)AMINO]PROPAN 2 OL; 1 [[(1 BENZYL 3,5 DIMETHYL 1H PYRAZOL 4 YL)METHYL](METHYL)AMINO] 3 PHENOXYPROPAN 2 OL; 1 [[1 (2 CHLOROBENZYL) 3,5 DIMETHYL 1H PYRAZOL 4 YL]METHYL](METHYL)AMINO 3 (4 CHLOROPHENOXY)PROPAN 2 OL; 1 [[[1 (2 CHLOROBENZYL) 3,5 DIMETHYL 1H PYRAZOL 4 YL]METHYL](METHYL)AMINO] 3 (4 ETHOXYPHENOXY)PROPAN 2 OL; AMINOALCOHOL; ANTIINFECTIVE AGENT; BETA AMINOALCOHOL DERIVATIVE; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BLOOD BRAIN BARRIER; CHIRALITY; CONTROLLED STUDY; DRUG METABOLISM; DRUG SOLUBILITY; DRUG SYNTHESIS; EX VIVO STUDY; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; INFLAMMATION; MACROPHAGE; NONHUMAN; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

AMINO ALCOHOLS; ANIMALS; ANTI-INFLAMMATORY AGENTS; BLOOD-BRAIN BARRIER; CELL LINE, TUMOR; HUMANS; LIPOPOLYSACCHARIDES; MACROPHAGE ACTIVATION; MICE; MODELS, MOLECULAR; NITRIC OXIDE; PERMEABILITY; SEPSIS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TOLL-LIKE RECEPTOR 4;

EID: 79960169180     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2003365     Document Type: Article

References (44)

1. Takeda, K.; Akira, S. Toll-like receptors in innate immunity Int. Immunol. 2005, 17, 1-14
2. Fitzgerald, K. A.; Rowe, D. C.; Golenbock, D. T. Endotoxin recognition and signal transduction by the TLR4/MD2-complex Microbes Infect. 2004, 6, 1361-1367 (Pubitemid 41110578)
3. Park, B. S.; Song, D. H.; Kim, H. M.; Choi, B. S.; Lee, H.; Lee, J. O. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex Nature 2009, 458, 1191-1195
4. Matzinger, P. The danger model: a renewed sense of self Science 2002, 296, 301-305 (Pubitemid 34303674)
5. Lehnardt, S.; Massillon, L.; Follett, P.; Jensen, F. E.; Ratan, R.; Rosenberg, P. A.; Volpe, J. J.; Vartanian, T. Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 8514-8519 (Pubitemid 36842576)
6. Peri, F.; Piazza, M.; Calabrese, V.; Damore, G.; Cighetti, R. Exploring the LPS/TLR4 signal pathway with small molecules Biochem. Soc. Trans. 2010, 38, 1390-1395
7. Wittebole, X.; Castanares-Zapatero, D.; Laterre, P. F. Toll-like receptor 4 modulation as a strategy to treat sepsis Mediators Inflammation 2010, 2010, 568396
8. Guo, L. H.; Schluesener, H. J. The innate immunity of the central nervous system in chronic pain: the role of Toll-like receptors Cell. Mol. Life Sci. 2007, 64, 1128-1136 (Pubitemid 46684548)
9. Tanga, F. Y.; Nutile-McMenemy, N.; DeLeo, J. A. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 5856-5861 (Pubitemid 40559649)
10. Leon, C. G.; Tory, R.; Jia, J.; Sivak, O.; Wasan, K. M. Discovery and development of Toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases Pharm. Res. 2008, 25, 1751-1761
11. Qu, J.; Zhang, J.; Pan, J.; He, L.; Ou, Z.; Zhang, X.; Chen, X. Endotoxin tolerance inhibits lipopolysaccharide-initiated acute pulmonary inflammation and lung injury in rats by the mechanism of nuclear factor-kappaB Scand. J. Immunol. 2003, 58, 613-619 (Pubitemid 37521936)
12. Johnson, D. A. Synthetic TLR4-active glycolipids as vaccine adjuvants and stand-alone immunotherapeutics Curr. Top. Med. Chem. 2008, 8, 64-79 (Pubitemid 351791032)
13. Meng, J.; Lien, E.; Golenbock, D. T. MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation J. Biol. Chem. 2010, 285, 8695-8702
14. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 2001, 46, 3-26 (Pubitemid 33653411)
15. Yin, H.; Hamilton, A. D. Strategies for targeting protein-protein interactions with synthetic agents Angew. Chem., Int. Ed. 2005, 44, 4130-4163 (Pubitemid 40982718)
16. Park, S. J.; Kang, S. H.; Kang, Y. K.; Eom, Y. B.; Koh, K. O.; Kim, D. Y.; Youn, H. S. Inhibition of homodimerization of Toll-like receptor 4 by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester Int. Immunopharmacol. 2011, 11, 19-22
17. Jin, G. H.; Li, H.; An, S.; Ryu, J. H.; Jeon, R. Design, synthesis and activity of benzothiazole-based inhibitors of NO production in LPS-activated macrophages Bioorg. Med. Chem. Lett. 2010, 20, 6199-6202
18. Kawamoto, T.; Ii, M.; Kitazaki, T.; Iizawa, Y.; Kimura, H. TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain Eur. J. Pharmacol. 2008, 584, 40-48
19. Takashima, K.; Matsunaga, N.; Yoshimatsu, M.; Hazeki, K.; Kaisho, T.; Uekata, M.; Hazeki, O.; Akira, S.; Iizawa, Y.; Ii, M. Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model Br. J. Pharmacol. 2009, 157, 1250-1262
20. Rice, T. W.; Wheeler, A. P.; Bernard, G. R.; Vincent, J. L.; Angus, D. C.; Aikawa, N.; Demeyer, I.; Sainati, S.; Amlot, N.; Cao, C.; Ii, M.; Matsuda, H.; Mouri, K.; Cohen, J. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis Crit. Care Med. 2010, 38, 1685-1694
21. Matsunaga, N.; Tsuchimori, N.; Matsumoto, T.; Ii, M. TAK-242 (resatorvid), a small-molecule inhibitor of TLR4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules Mol. Pharmacol. 2011, 79, 34-41
22. Bevan, D. E.; Martinko, A. J.; Loram, L. C.; Stahl, J. A.; Taylor, F. R.; Joshee, S.; Watkins, L. R.; Yin, H. Selection, preparation, and evaluation of small-molecule inhibitors of Toll-like receptor 4 ACS Med. Chem. Lett. 2010, 1, 194-198
23. Joce, C.; Stahl, J. A.; Shridhar, M.; Hutchinson, M. R.; Watkins, L. R.; Fedichev, P. O.; Yin, H. Application of a novel in silico high-throughput screen to identify selective inhibitors for protein-protein interactions Bioorg. Med. Chem. Lett. 2010, 20, 5411-5413
24. Bevinakatti, H. S.; Banerji, A. A. Lipase catalysis in organic solvents. Application to the synthesis of (R)-and (S)-atenololt J. Org. Chem. 1992, 57, 6003-6005
25. Lee, K. C.; Moon, B. S.; Lee, J. H.; Chung, K.-H.; Katzenellenbogen, J. A.; Chi, D. Y. Synthesis and binding affinities of fluoroalkylated raloxifenes Bioorg. Med. Chem. Lett. 2003, 11, 3649-3658 (Pubitemid 36952263)
26. Wipf, P.; Weiner, W., S. Enantioselective synthesis and photoracemization studies of (+)-2-cyclopropyl-7,8-dimethoxy-2 H -chromene-5-carboxylic acid methyl ester, an advanced intermediate of a dihydrofolate reductase inhibitor J. Org. Chem. 1999, 64, 5321-5324
27. Butera, J. A.; Spinelli, W.; Anantharaman, V.; Marcopulos, N.; Parsons, R. W.; Moubarak, I. F.; Cullinan, C.; Baglit, J. F. Synthesis and selective class III antiarrhythmic activity of novel N-heteroaralkyl-substituted 1-(aryloxy)-2-propanolamine and related propylamine derivatives J. Med. Chem. 1991, 34, 3212-3228
28. Bevan, D. E. Selection, Preparation, and Evaluation of Inhibitors of Toll-like Receptor 4. M.S. Thesis, University of Colorado at Boulder, Boulder, CO, U.S., 2010.
29. Robin, A.; Brown, F.; Bahamontes-Rosa, N.; Wu, B.; Beitz, E.; Kun, J. F. J.; Flitsch, S. L. Microwave-assisted ring opening of epoxides: a general route to the synthesis of 1-aminopropan-2-ols with anti-malaria parasite activities J. Med. Chem. 2007, 50, 4243-4249 (Pubitemid 47301755)
30. Lober, S.; Ortner, B.; Bettinetti, L.; Hubnee, H.; Gmeiner, P. Analogs of the dopamine D4 receptor ligand FAUC 113 with planar- and central-chirality Tetrahedron: Asymmetry 2002, 13, 2303-2310 (Pubitemid 35336042)
31. Kemper, S.; Hrobarik, P.; Kaupp, M.; Schlorer, N. E. Jacobsen's catalyst for hydrolytic kinetic resolution: structure elucidation of paramagnetic Co(III)-Salen complexes in solution via combined NMR and quantum chemical studies J. Am. Chem. Soc. 2009, 131, 4172-4173
32. Schaus, S. E.; Brandes, B., D.; Larrow, J., F.; Tokunaga, M.; Hansen, K., B.; Gould, A., E.; Furrow, M., E.; Jacobsen, E., N. Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)CoIII complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols J. Am. Chem. Soc. 2002, 124, 1307-1315 (Pubitemid 34169137)
33. Ready, J. M.; Jacobsen, E., N. Highly active oligomeric (salen)-Co catalysts for asymmetric epoxide ring-opening reactions J. Am. Chem. Soc. 2001, 123, 2687-2688 (Pubitemid 32888579)
34. Kang, B.; Chang, S. A facile synthetic route to (+)-allosedamine via hydrolytic kinetic resolution and olefin metathesis Tetrahedron 2004, 60, 7353-7359 (Pubitemid 39055938)
35. Pérez de Vega, M. J.; García-Aranda, M. I.; González-Muñiz, R. A role for ring-closing metathesis in medicinal chemistry: mimicking secondary architectures in bioactive peptides. Med. Res. Rev. [Online early access] DOI: 10.1002/med.20199. Published Online: Jan 14, 2010.
36. Fu, G., C.; Nguyen, S., T.; Grubbs, R., H. Catalytic ring-closing metathesis of functionalized dienes by a ruthenium carbene complex J. Am. Chem. Soc. 1993, 115, 9856-9857
37. Peng, Z. R.; Zhong, W. H.; Liu, J.; Xiao, P. T. Effects of the combination of hyperbaric oxygen and 5-fluorouracil on proliferation and metastasis of human nasopharyngeal carcinoma CNE-2Z cells Undersea Hyperbaric Med. 2010, 37, 141-150
38. Di, L. Profiling drug-like properties in discovery research Curr. Opin. Chem. Biol. 2003, 7, 402-408 (Pubitemid 36782368)
39. Mollnes, T. E.; Brekke, O. L.; Fung, M.; Fure, H.; Christiansen, D.; Bergseth, B.; Videm, V.; Lappegård, K. T.; Köhl, J.; Lambris, J. Essential role of the C5a receptor in E coli -induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation Blood 2002, 100, 1869-1877 (Pubitemid 34925168)
40. Fletcher, S.; Turkson, J.; Gunning, P. T. Molecular approaches towards the inhibition of the signal transducer and activator of transcription 3 (Stat3) protein ChemMedChem 2008, 3, 1159-1168
41. Wilson, A., J. Inhibition of protein-protein interactions using designed molecules Chem. Soc. Rev. 2009, 38, 3289-3300
42. Misko, T. P.; Schilling, R. J.; Salvemini, D.; Moore, W. M.; Currie, M. G. A fluorometric assay for the measurement of nitrite in biological samples Anal. Biochem. 1993, 214, 11-16 (Pubitemid 23300346)
43. Nussler, A. K.; Glanemann, M.; Schirmeier, A.; Liu, L.; Nussler, N. C. Fluorometric measurement of nitrite/nitrate by 2,3-diaminonaphthalene Nat. Protoc. 2006, 1, 2223-2226
44. Jester, B. W.; Cox, K. J.; Gaj, A.; Shomin, C. D.; Porter, J. R.; Ghosh, I. A coiled-coil enabled split-luciferase three-hybrid system: applied toward profiling inhibitors of protein kinases J. Am. Chem. Soc. 2010, 132, 11727-11735