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Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity.

DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cee VJ, Chai L, Deak HL, Epstein LF, Faust T, Gallant P, Geuns-Meyer SD, Gore A, Gu Y, Henkle B, Hodous BL, Hsieh F, Huang X, Kim JL, Lee JH, Martin MW, Masse CE, McGowan DC, Metz D, Mohn D, Morgenstern KA, Oliveira-dos-Santos A, Patel VF, Powers D, Rose PE, Schneider S, Tomlinson SA, Tudor YY, Turci SM, Welcher AA, White RD, Zhao H, Zhu L, Zhu X
J Med Chem 49 5671-86 (2006)
Cited: 35 times
EuropePMC logo PMID: 16970394

Abstract

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED(50) of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

Articles - 2og8 mentioned but not cited (7)

  1. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, Peterson JR, Dunbrack RL. Sci Signal 8 rs13 (2015)
  2. DFGmodel: predicting protein kinase structures in inactive states for structure-based discovery of type-II inhibitors. Ung PM, Schlessinger A. ACS Chem Biol 10 269-278 (2015)
  3. Predicting inactive conformations of protein kinases using active structures: conformational selection of type-II inhibitors. Xu M, Yu L, Wan B, Yu L, Huang Q. PLoS One 6 e22644 (2011)
  4. Identification of Druggable Kinase Target Conformations Using Markov Model Metastable States Analysis of apo-Abl. Paul F, Meng Y, Roux B. J Chem Theory Comput 16 1896-1912 (2020)
  5. Computational analysis of kinase inhibitor selectivity using structural knowledge. Lo YC, Liu T, Morrissey KM, Kakiuchi-Kiyota S, Johnson AR, Broccatelli F, Zhong Y, Joshi A, Altman RB. Bioinformatics 35 235-242 (2019)
  6. Data-Driven Construction of Antitumor Agents with Controlled Polypharmacology. Da C, Zhang D, Stashko M, Vasileiadi E, Parker RE, Minson KA, Huey MG, Huelse JM, Hunter D, Gilbert TSK, Norris-Drouin J, Miley M, Herring LE, Graves LM, DeRyckere D, Earp HS, Graham DK, Frye SV, Wang X, Kireev D. J Am Chem Soc 141 15700-15709 (2019)
  7. Investigating the effect of Icaritin on hepatocellular carcinoma based on network pharmacology. Xue Z, Zhang F, Xu S, Chen M, Wang M, Wang M, Ke F, Chen Z, Zhang M. Front Pharmacol 14 1208495 (2023)


Reviews citing this publication (3)

  1. Update on lymphocyte specific kinase inhibitors: a patent survey. Martin MW, Machacek MR. Expert Opin Ther Pat 20 1573-1593 (2010)
  2. New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011-2021) focussing on structure-activity relationship (SAR) and docking insights. Elkamhawy A, Ali EMH, Lee K. J Enzyme Inhib Med Chem 36 1574-1602 (2021)
  3. T-cell-targeted signaling inhibitors. Won J, Lee GH. Int Rev Immunol 27 19-41 (2008)

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  2. Small molecule recognition of c-Src via the Imatinib-binding conformation. Dar AC, Lopez MS, Shokat KM. Chem Biol 15 1015-1022 (2008)
  3. Sequence determinants of a specific inactive protein kinase conformation. Hari SB, Merritt EA, Maly DJ. Chem Biol 20 806-815 (2013)
  4. Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases. Link W, Oyarzabal J, Serelde BG, Albarran MI, Rabal O, Cebriá A, Alfonso P, Fominaya J, Renner O, Peregrina S, Soilán D, Ceballos PA, Hernández AI, Lorenzo M, Pevarello P, Granda TG, Kurz G, Carnero A, Bischoff JR. J Biol Chem 284 28392-28400 (2009)
  5. Small-molecule inhibitors binding to protein kinase. Part II: the novel pharmacophore approach of type II and type III inhibition. Backes A, Zech B, Felber B, Klebl B, Müller G. Expert Opin Drug Discov 3 1427-1449 (2008)
  6. Kinase inhibitors for the treatment of inflammatory and autoimmune disorders. Bhagwat SS. Purinergic Signal 5 107-115 (2009)
  7. Affinity-based probes based on type II kinase inhibitors. Ranjitkar P, Perera BG, Swaney DL, Hari SB, Larson ET, Krishnamurty R, Merritt EA, Villén J, Maly DJ. J Am Chem Soc 134 19017-19025 (2012)
  8. Affinity reagents that target a specific inactive form of protein kinases. Ranjitkar P, Brock AM, Maly DJ. Chem Biol 17 195-206 (2010)
  9. Conformation-selective inhibitors reveal differences in the activation and phosphate-binding loops of the tyrosine kinases Abl and Src. Hari SB, Perera BG, Ranjitkar P, Seeliger MA, Maly DJ. ACS Chem Biol 8 2734-2743 (2013)
  10. Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cheng A, Faust T, Hsieh F, Huang X, Lee JH, Marshall TL, Martin MW, McGowan DC, Schneider S, Turci SM, White RD, Zhu X. Bioorg Med Chem Lett 17 2305-2309 (2007)
  11. Strong nonadditivity as a key structure-activity relationship feature: distinguishing structural changes from assay artifacts. Kramer C, Fuchs JE, Liedl KR. J Chem Inf Model 55 483-494 (2015)
  12. Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: design, synthesis and biological evaluation. Wang C, Gao H, Dong J, Zhang Y, Su P, Shi Y, Zhang J. Bioorg Med Chem 22 277-284 (2014)
  13. Exploring conformational search protocols for ligand-based virtual screening and 3-D QSAR modeling. Cappel D, Dixon SL, Sherman W, Duan J. J Comput Aided Mol Des 29 165-182 (2015)
  14. Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties. Martin MW, Newcomb J, Nunes JJ, Bemis JE, McGowan DC, White RD, Buchanan JL, DiMauro EF, Boucher C, Faust T, Hsieh F, Huang X, Lee JH, Schneider S, Turci SM, Zhu X. Bioorg Med Chem Lett 17 2299-2304 (2007)
  15. Targeting the unactivated conformations of protein kinases for small molecule drug discovery. Alton GR, Lunney EA. Expert Opin Drug Discov 3 595-605 (2008)
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  17. NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. Tröster A, Heinzlmeir S, Berger BT, Gande SL, Saxena K, Sreeramulu S, Linhard V, Nasiri AH, Bolte M, Müller S, Kuster B, Médard G, Kudlinzki D, Schwalbe H. ChemMedChem 13 1629-1633 (2018)
  18. Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR. Takayama T, Umemiya H, Amada H, Yabuuchi T, Shiozawa F, Katakai H, Takaoka A, Yamaguchi A, Endo M, Sato M. Bioorg Med Chem Lett 20 108-111 (2010)
  19. Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-specific kinase (Lck): Structure, synthesis, and SAR. Takayama T, Umemiya H, Amada H, Yabuuchi T, Koami T, Shiozawa F, Oka Y, Takaoka A, Yamaguchi A, Endo M, Sato M. Bioorg Med Chem Lett 20 112-116 (2010)
  20. The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL. Jacobsen AV, Pierotti CL, Lowes KN, Au AE, Zhang Y, Etemadi N, Fitzgibbon C, Kersten WJA, Samson AL, van Delft MF, Huang DCS, Sabroux HJ, Lessene G, Silke J, Murphy JM. Cell Death Dis 13 291 (2022)
  21. N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR. Deak HL, Newcomb JR, Nunes JJ, Boucher C, Cheng AC, DiMauro EF, Epstein LF, Gallant P, Hodous BL, Huang X, Lee JH, Patel VF, Schneider S, Turci SM, Zhu X. Bioorg Med Chem Lett 18 1172-1176 (2008)
  22. Synthesis of some novel dibromo-2-arylquinazolinone derivatives as cytotoxic agents. Faghih Z, Rahmannejadi N, Sabet R, Zomorodian K, Asad M, Khabnadideh S. Res Pharm Sci 14 115-121 (2019)
  23. The chemistry and pharmacology of privileged pyrroloquinazolines. Chao B, Li BX, Xiao X. Medchemcomm 6 510-520 (2015)
  24. QM/QM docking method based on the variational finite localized molecular orbital approximation. Anisimov VM, Bugaenko VL. J Comput Chem 30 784-798 (2009)
  25. The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-β production in regulatory T-cells. Kagawa K, Sato S, Koyama K, Imakura T, Murakami K, Yamashita Y, Naito N, Ogawa H, Kawano H, Nishioka Y. PLoS One 17 e0275987 (2022)


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