Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

N,N-Disubstituted 4-sulfamoylbenzoic Cid Derivatives as Inhibitors of Cytosolic Phospholipase A2α: Synthesis, Aqueous Solubility, and Activity in a Vesicle and a Whole Blood Assay

In Press, (this is not the final "Version of Record"). Available online 22 July, 2024
Author(s): Daniel Borecki, Imke Meyer zu Vilsendorf, Jörg Fabian and Matthias Lehr*
Published on: 22 July, 2024

DOI: 10.2174/0115734064320241240709114041

Price: $95

Abstract

Background: Cytosolic phospholipase A2α (cPLA2α) is the key enzyme that initiates the arachidonic acid cascade through which proinflammatory lipid mediators can be formed. Therefore, cPLA2α is considered an interesting target for the development of anti-inflammatory drugs. Although several effective inhibitors of the enzyme have been developed, none of them has yet reached clinical application.

Objective: Recently, we have prepared new 4-sulfamoylbenzoic acid derivatives based on a cPLA2α inhibitor found in a ligand-based virtual screening. The most effective of these compounds were now subjected to further variations in which the substitution pattern on the sulfamoyl nitrogen atom was changed.

Methods: The new compounds were tested in vitro in a vesicle assay for cPLA2α inhibition as well as for their water solubility, metabolic stability, and selectivity towards related enzymes. In addition, they were evaluated ex vivo in a whole blood assay in which metabolites of the arachidonic acid cascade formed after activation of cPLA2α were quantified using a combined online dilution/online solid phase extraction HPLC-MS method.

Results: Inhibitors with submicromolar inhibitory in vitro potency were found with favourable water solubility and selectivity. However, their efficacy did not match that of the highly effective, known, structurally related cPLA2a inhibitor giripladib, which was also tested as a reference. One advantage of some of the new compounds compared to giripladib was their significantly improved water solubility. When analyzing the substances in the ex vivo whole blood assay, it was found that the obtained inhibition data correlated better with the in vivo results when the phorbol ester 12-Otetradecanoylphorbol-13-acetate was used for activation of the enzyme in the blood cells instead of the calcium ionophore A23187.

Conclusion: New compounds with good activity towards cPLA2α and reasonable physicochemical properties were identified. Overall, the results obtained could be helpful in the development of clinically applicable inhibitors of this enzyme.

[1]
Lee, C.W.; Lin, C.C.; Lee, I.T.; Lee, H.C.; Yang, C.M. Activation and induction of cytosolic phospholipase A2 by TNF‐α mediated through Nox2, MAPKs, NF‐κB, and p300 in human tracheal smooth muscle cells. J. Cell. Physiol., 2011, 226(8), 2103-2114.
[http://dx.doi.org/10.1002/jcp.22537] [PMID: 21520062]
[2]
Lee, C.W.; Lee, I.T.; Lin, C.C.; Lee, H.C.; Lin, W.N.; Yang, C.M. Activation and induction of cytosolic phospholipase A2 by IL‐1β in human tracheal smooth muscle cells: Role of MAPKs/p300 and NF‐κB. J. Cell. Biochem., 2010, 109(5), 1045-1056.
[http://dx.doi.org/10.1002/jcb.22488] [PMID: 20069553]
[3]
Newton, R.; Kuitert, L.M.; Slater, D.M.; Adcock, I.M.; Barnes, P.J. Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells. Life Sci., 1996, 60(1), 67-78.
[http://dx.doi.org/10.1016/S0024-3205(96)00590-5] [PMID: 8995534]
[4]
Clark, J.D.; Lin, L.L.; Kriz, R.W.; Ramesha, C.S.; Sultzman, L.A.; Lin, A.Y.; Milona, N.; Knopf, J.L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell, 1991, 65(6), 1043-1051.
[http://dx.doi.org/10.1016/0092-8674(91)90556-E] [PMID: 1904318]
[5]
Dessen, A. Structure and mechanism of human cytosolic phospholipase A2. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2000, 1488(1-2), 40-47.
[http://dx.doi.org/10.1016/S1388-1981(00)00108-6] [PMID: 11080675]
[6]
Shimizu, T.; Wolfe, L.S. Arachidonic acid cascade and signal transduction. J. Neurochem., 1990, 55(1), 1-15.
[http://dx.doi.org/10.1111/j.1471-4159.1990.tb08813.x] [PMID: 2113081]
[7]
Ricciotti, E.; FitzGerald, G.A. Prostaglandins and inflammation. Arterioscler. Thromb. Vasc. Biol., 2011, 31(5), 986-1000.
[http://dx.doi.org/10.1161/ATVBAHA.110.207449] [PMID: 21508345]
[8]
Yokomizo, T.; Izumi, T.; Shimizu, T. Leukotriene B4: Metabolism and signal transduction. Arch. Biochem. Biophys., 2001, 385(2), 231-241.
[http://dx.doi.org/10.1006/abbi.2000.2168] [PMID: 11368003]
[9]
Wahid, H.H.; Anahar, F.N.; Isahak, N.H.; Zoharodzi, J.M.; Lina Mohammad Khoiri, S.N.; Mohamad Zainal, N.H.; Kamarudin, N.; Ismail, H.; Al-Deen Mustafa Mahmud, M.I. Role of platelet activating factor as a mediator of inflammatory diseases and preterm delivery. Am. J. Pathol., 2024, 194(6), 862-878.
[http://dx.doi.org/10.1016/j.ajpath.2024.01.018]
[10]
Uozumi, N.; Kume, K.; Nagase, T.; Nakatani, N.; Ishii, S.; Tashiro, F.; Komagata, Y.; Maki, K.; Ikuta, K.; Ouchi, Y.; Miyazaki, J.; Shimizu, T. Role of cytosolic phospholipase A2 in allergic response and parturition. Nature, 1997, 390(6660), 618-622.
[http://dx.doi.org/10.1038/37622] [PMID: 9403692]
[11]
Bonventre, J.V.; Huang, Z.; Taheri, M.R.; O’Leary, E.; Li, E.; Moskowitz, M.A.; Sapirstein, A. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature, 1997, 390(6660), 622-625.
[http://dx.doi.org/10.1038/37635] [PMID: 9403693]
[12]
Hegen, M.; Sun, L.; Uozumi, N.; Kume, K.; Goad, M.E.; Nickerson-Nutter, C.L.; Shimizu, T.; Clark, J.D. Cytosolic phospholipase A2α-deficient mice are resistant to collagen-induced arthritis. J. Exp. Med., 2003, 197(10), 1297-1302.
[http://dx.doi.org/10.1084/jem.20030016] [PMID: 12743172]
[13]
Ghosh, M.; Tucker, D.; Burchett, S.; Leslie, C. Properties of the group IV phospholipase A2 family. Prog. Lipid Res., 2006, 45(6), 487-510.
[http://dx.doi.org/10.1016/j.plipres.2006.05.003] [PMID: 16814865]
[14]
Niknami, M.; Patel, M.; Witting, P.K.; Dong, Q. Molecules in focus: Cytosolic phospholipase A2-α. Int. J. Biochem. Cell Biol., 2009, 41(5), 994-997.
[http://dx.doi.org/10.1016/j.biocel.2008.07.017] [PMID: 18761105]
[15]
Linkous, A.; Yazlovitskaya, E. Cytosolic phospholipase A2 as a mediator of disease pathogenesis. Cell. Microbiol., 2010, 12(10), 1369-1377.
[http://dx.doi.org/10.1111/j.1462-5822.2010.01505.x] [PMID: 20642808]
[16]
Leslie, C.C. Cytosolic phospholipase A2: physiological function and role in disease. J. Lipid Res., 2015, 56(8), 1386-1402.
[http://dx.doi.org/10.1194/jlr.R057588] [PMID: 25838312]
[17]
Kita, Y.; Shindou, H.; Shimizu, T. Cytosolic phospholipase A2 and lysophospholipid acyltransferases. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2019, 1864(6), 838-845.
[http://dx.doi.org/10.1016/j.bbalip.2018.08.006] [PMID: 30905348]
[18]
Lehr, M. Inhibitors of cytosolic phospholipase A2α as potential anti-inflammatory drugs. Antiinflamm. Antiallergy Agents Med. Chem., 2006, 5(2), 149-161.
[http://dx.doi.org/10.2174/187152306776872488]
[19]
Soubhye, J.; van Antwerpen, P.; Dufrasne, F. Targeting cytosolic phospholipase A2α for novel anti-inflammatory agents. Curr. Med. Chem., 2018, 25(21), 2418-2447.
[http://dx.doi.org/10.2174/0929867325666180117103919] [PMID: 29345571]
[20]
Batsika, C.S.; Gerogiannopoulou, A.D.D.; Mantzourani, C.; Vasilakaki, S.; Kokotos, G. The design and discovery of phospholipase A2 inhibitors for the treatment of inflammatory diseases. Expert Opin. Drug Discov., 2021, 16(11), 1287-1305.
[http://dx.doi.org/10.1080/17460441.2021.1942835] [PMID: 34143707]
[21]
McKew, J.C.; Foley, M.A.; Thakker, P.; Behnke, M.L.; Lovering, F.E.; Sum, F.W.; Tam, S.; Wu, K.; Shen, M.W.H.; Zhang, W.; Gonzalez, M.; Liu, S.; Mahadevan, A.; Sard, H.; Khor, S.P.; Clark, J.D. Inhibition of cytosolic phospholipase A2α: hit to lead optimization. J. Med. Chem., 2006, 49(1), 135-158.
[http://dx.doi.org/10.1021/jm0507882] [PMID: 16392799]
[22]
McKew, J.C.; Lee, K.L.; Shen, M.W.; Thakker, P.; Foley, M.A.; Behnke, M.L.; Hu, B.; Sum, F.W.; Tam, S.; Hu, Y.; Chen, L.; Kirincich, S.J.; Michalak, R.; Thomason, J.; Ipek, M.; Wu, K.; Wooder, L.; Ramarao, M.K.; Murphy, E.A.; Goodwin, D.G.; Albert, L.; Xu, X.; Donahue, F.; Ku, M.S.; Keith, J.; Nickerson-Nutter, C.L.; Abraham, W.M.; Williams, C.; Hegen, M.; Clark, J.D. Indole cytosolic Phospholipase A2 a inhibitors: Discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic acid, efipladib. J. Med. Chem., 2008, 51(12), 3388-3413.
[http://dx.doi.org/10.1021/jm701467e] [PMID: 18498150]
[23]
McKew, J. C.; Lee, K. L.; Chen, L.; Vargas, R.; Clark, J. D.; Williams, C.; Clerin, V.; Marusic, S.; Pong, K. Inhibitors of cytosolic phospholipase. WO2006/128142A2, 2006.
[24]
Tomoo, T.; Nakatsuka, T.; Katayama, T.; Hayashi, Y.; Fujieda, Y.; Terakawa, M.; Nagahira, K. Design, synthesis, and biological evaluation of 3-(1-Aryl-1H-indol-5-yl)propanoic acids as new indole-based cytosolic phospholipase A2α inhibitors. J. Med. Chem., 2014, 57(17), 7244-7262.
[http://dx.doi.org/10.1021/jm500494y] [PMID: 25102418]
[25]
Kozaki, T.; Tagashira, M.; Yamanishi, K.; Ellis, B.; Kayanoki, T.; Ooishi, R.; Sugiyama, K.; Matsuda, S.; Tsuruta, K.; Kohira, T.; Tsurui, K. Evaluation of drug–drug interaction between the novel cPLA2 inhibitor AK106-001616 and methotrexate in rheumatoid arthritis patients. Xenobiotica, 2015, 45(7), 615-624.
[http://dx.doi.org/10.3109/00498254.2014.1000430] [PMID: 25579091]
[26]
Ono, T.; Yamada, K.; Chikazawa, Y.; Ueno, M.; Nakamoto, S.; Okuno, T.; Seno, K. Characterization of a novel inhibitor of cytosolic phospholipase A2α, pyrrophenone. Biochem. J., 2002, 363(3), 727-735.
[http://dx.doi.org/10.1042/bj3630727] [PMID: 11964173]
[27]
Seno, K.; Okuno, T.; Nishi, K.; Murakami, Y.; Watanabe, F.; Matsuura, T.; Wada, M.; Fujii, Y.; Yamada, M.; Ogawa, T.; Okada, T.; Hashizume, H.; Kii, M.; Hara, S.; Hagishita, S.; Nakamoto, S.; Yamada, K.; Chikazawa, Y.; Ueno, M.; Teshirogi, I.; Ono, T.; Ohtani, M. Pyrrolidine inhibitors of human cytosolic phospholipase A2. J. Med. Chem., 2000, 43(6), 1041-1044.
[http://dx.doi.org/10.1021/jm9905155] [PMID: 10737736]
[28]
Connolly, S.; Bennion, C.; Botterell, S.; Croshaw, P.J.; Hallam, C.; Hardy, K.; Hartopp, P.; Jackson, C.G.; King, S.J.; Lawrence, L.; Mete, A.; Murray, D.; Robinson, D.H.; Smith, G.M.; Stein, L.; Walters, I.; Wells, E.; Withnall, W.J. Design and synthesis of a novel and potent series of inhibitors of cytosolic phospholipase A2 based on a 1,3-disubstituted propan-2-one skeleton. J. Med. Chem., 2002, 45(6), 1348-1362.
[http://dx.doi.org/10.1021/jm011050x] [PMID: 11882004]
[29]
Ludwig, J.; Bovens, S.; Brauch, C.; Elfringhoff, A.S.; Lehr, M. Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human cytosolic phospholipase A2α. J. Med. Chem., 2006, 49(8), 2611-2620.
[http://dx.doi.org/10.1021/jm051243a] [PMID: 16610804]
[30]
Drews, A.; Bovens, S.; Roebrock, K.; Sunderkötter, C.; Reinhardt, D.; Schäfers, M.; van der Velde, A.; Schulze Elfringhoff, A.; Fabian, J.; Lehr, M. 1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A2α with reduced lipophilicity: synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activity. J. Med. Chem., 2010, 53(14), 5165-5178.
[http://dx.doi.org/10.1021/jm1001088] [PMID: 20583844]
[31]
Mete, A.; Andrews, G.; Bernstein, M.; Connolly, S.; Hartopp, P.; Jackson, C.G.; Lewis, R.; Martin, I.; Murray, D.; Riley, R.; Robinson, D.H.; Smith, G.M.; Wells, E.; Withnall, W.J. Design of novel and potent cPLA2α inhibitors containing an α-methyl-2-ketothiazole as a metabolically stable serine trap. Bioorg. Med. Chem. Lett., 2011, 21(10), 3128-3133.
[http://dx.doi.org/10.1016/j.bmcl.2011.03.005] [PMID: 21450464]
[32]
Kokotos, G.; Kotsovolou, S.; Six, D.A.; Constantinou-Kokotou, V.; Beltzner, C.C.; Dennis, E.A. Novel 2-oxoamide inhibitors of human group IVA phospholipase A2. J. Med. Chem., 2002, 45(14), 2891-2893.
[http://dx.doi.org/10.1021/jm025538p] [PMID: 12086476]
[33]
Psarra, A.; Kokotou, M.G.; Galiatsatou, G.; Mouchlis, V.D.; Dennis, E.A.; Kokotos, G. Highly potent 2-oxoester inhibitors of cytosolic phospholipase A2 (GIVA cPLA2). ACS Omega, 2018, 3(8), 8843-8853.
[http://dx.doi.org/10.1021/acsomega.8b01214] [PMID: 30197994]
[34]
Kokotou, M.G.; Galiatsatou, G.; Magrioti, V.; Koutoulogenis, G.; Barbayianni, E.; Limnios, D.; Mouchlis, V.D.; Satpathy, B.; Navratil, A.; Dennis, E.A.; Kokotos, G. 2-Oxoesters: A novel class of potent and selective inhibitors of cytosolic group IVA phospholipase A2. Sci. Rep., 2017, 7(1), 7025.
[http://dx.doi.org/10.1038/s41598-017-07330-5] [PMID: 28765606]
[35]
Yamanishi, K.; Ellis, B.; Kudo, K.; Kayanoki, T.; Dews, I.; Ostor, A.; Wilson, A. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann. Rheum. Dis., 2013, 73(3), 492-509.
[http://dx.doi.org/10.1136/annrheumdis-2013-eular.751]
[36]
Kirincich, S.J.; Xiang, J.; Green, N.; Tam, S.; Yang, H.Y.; Shim, J.; Shen, M.W.H.; Clark, J.D.; McKew, J.C. Benzhydrylquinazolinediones: Novel cytosolic phospholipase A2α inhibitors with improved physicochemical properties. Bioorg. Med. Chem., 2009, 17(13), 4383-4405.
[http://dx.doi.org/10.1016/j.bmc.2009.05.027] [PMID: 19482480]
[37]
Walters, I.; Bennion, C.; Connolly, S.; Croshaw, P.J.; Hardy, K.; Hartopp, P.; Jackson, C.G.; King, S.J.; Lawrence, L.; Mete, A.; Murray, D.; Robinson, D.H.; Stein, L.; Wells, E.; John Withnall, W. Synthesis and evaluation of substrate-mimicking cytosolic phospholipase A2 inhibitors reducing the lipophilicity of the arachidonyl chain isostere. Bioorg. Med. Chem. Lett., 2004, 14(14), 3645-3649.
[http://dx.doi.org/10.1016/j.bmcl.2004.05.024] [PMID: 15203135]
[38]
Garzinsky, D. Cytosolic phospholipase A2α and fatty acid amide hydrolase as potential drug targets: Synthesis and testing of inhibitors and identification of new lead structures by computer-assisted drug design. Ph.D. Thesis; University of Münster: Münster, Germany, 2018. Available from: https://d-nb.info/1156953685
[39]
Borecki, D.; Lehr, M. N-Substituted 4-sulfamoylbenzoic acid derivatives as inhibitors of cytosolic phospholipase A2α. Med. Chem. Res., 2022, 31(6), 975-992.
[http://dx.doi.org/10.1007/s00044-022-02895-x]
[40]
Lipinski, C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 235-249.
[http://dx.doi.org/10.1016/S1056-8719(00)00107-6] [PMID: 11274893]
[41]
Valko, K.; Reynolds, D.P. High-throughput physicochemical and in vitro ADMET screening. Am. J. Drug Deliv., 2005, 3(2), 83-100.
[http://dx.doi.org/10.2165/00137696-200503020-00002]
[42]
Di Cesare, M. A.; Minetti, P.; Tarzia, G.; Spadoni, G. 5-Halotryptamine derivatives used as ligands of the 5HT6 and/or 5HT7 serotonin receptors. WO2003/000252A1, 2003.
[43]
Barth, M.; Rudolph, S.; Kampschulze, J.; Meyer zu Vilsendorf, I.; Hanekamp, W.; Mulac, D.; Langer, K.; Lehr, M. Hexafluoroisopropyl carbamates as selective MAGL and dual MAGL/FAAH inhibitors: Biochemical and physicochemical properties. ChemMedChem, 2022, 17(9), e202100757.
[http://dx.doi.org/10.1002/cmdc.202100757] [PMID: 35072346]
[44]
Finney, D.J. Probit Analysis: A Statistical treatment of the sigmoid response curve; Cambridge University Press: New York-London, 1952, pp. xvi-318.
[45]
Meyer zu Vilsendorf, I.; Einerhand, J.; Mulac, D.; Langer, K.; Lehr, M. 1-Benzylindoles as inhibitors of cytosolic phospholipase A2α: Synthesis, biological activity, aqueous solubility, and cell permeability. RSC Med. Chem., 2024, 15(2), 641-659.
[http://dx.doi.org/10.1039/D3MD00590A] [PMID: 38389890]
[46]
Schmitt, M.; Lehr, M. High-performance liquid chromatographic assay with ultraviolet spectrometric detection for the evaluation of inhibitors of secretory phospholipase A2. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 783(2), 327-333.
[http://dx.doi.org/10.1016/S1570-0232(02)00710-9] [PMID: 12482475]
[47]
Holtfrerich, A.; Hanekamp, W.; Lehr, M. (4-Phenoxyphenyl) tetrazolecarboxamides and related compounds as dual inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Eur. J. Med. Chem., 2013, 63, 64-75.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.050] [PMID: 23455058]
[48]
Holtfrerich, A.; Makharadze, T.; Lehr, M. High-performance liquid chromatography assay with fluorescence detection for the evaluation of inhibitors against human recombinant monoacylglycerol lipase. Anal. Biochem., 2010, 399(2), 218-224.
[http://dx.doi.org/10.1016/j.ab.2009.12.015] [PMID: 20015447]
[49]
Michels, G.; Lehr, M. High performance liquid chromatographic assays with UV-detection for evaluation of inhibitors of acetylcholinesterase and butyrylcholinesterase. J. Liqu. Chromatog. Rel. Technol., 2021, 44(5-6), 309-319.
[http://dx.doi.org/10.1080/10826076.2021.1925908]
[50]
Arnsmann, M.; Hanekamp, W.; Elfringhoff, A.S.; Lehr, M. Structure–activity relationship studies on 1-(2-oxopropyl)indole-5-carboxylic acids acting as inhibitors of cytosolic phospholipase A2α: Effect of substituents at the indole 3-position on activity, solubility, and metabolic stability. Eur. J. Med. Chem., 2017, 125, 1107-1114.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.039] [PMID: 27810597]
[51]
Subeska, A.; Althaus, J.; Hake, T.; Hanekamp, W.; Bettenworth, D.; Mulac, D.; Langer, K.; Lehr, M. Synthesis and pharmacokinetic properties of novel cPLA2α inhibitors with 1-(carboxyalkylpyrrolyl)-3-aryloxypropan-2-one structure. Bioorg. Med. Chem., 2023, 77, 117110.
[http://dx.doi.org/10.1016/j.bmc.2022.117110] [PMID: 36495814]
[52]
Hansford, K.A.; Reid, R.C.; Clark, C.I.; Tyndall, J.D.A.; Whitehouse, M.W.; Guthrie, T.; McGeary, R.P.; Schafer, K.; Martin, J.L.; Fairlie, D.P. D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with antiinflammatory activity. ChemBioChem, 2003, 4(2-3), 181-185.
[http://dx.doi.org/10.1002/cbic.200390029] [PMID: 12616631]
[53]
Ackermann, E.J.; Conde-Frieboes, K.; Dennis, E.A. Inhibition of macrophage Ca2+-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones. J. Biol. Chem., 1995, 270(1), 445-450.
[http://dx.doi.org/10.1074/jbc.270.1.445] [PMID: 7814408]
[54]
Johnson, D.S.; Stiff, C.; Lazerwith, S.E.; Kesten, S.R.; Fay, L.K.; Morris, M.; Beidler, D.; Liimatta, M.B.; Smith, S.E.; Dudley, D.T.; Sadagopan, N.; Bhattachar, S.N.; Kesten, S.J.; Nomanbhoy, T.K.; Cravatt, B.F.; Ahn, K. Discovery of PF-04457845: A highly potent, orally bioavailable, and selective urea FAAH inhibitor. ACS Med. Chem. Lett., 2011, 2(2), 91-96.
[http://dx.doi.org/10.1021/ml100190t] [PMID: 21666860]
[55]
Cisar, J.S.; Weber, O.D.; Clapper, J.R.; Blankman, J.L.; Henry, C.L.; Simon, G.M.; Alexander, J.P.; Jones, T.K.; Ezekowitz, R.A.B.; O’Neill, G.P.; Grice, C.A. Identification of ABX-1431, a selective inhibitor of monoacylglycerol lipase and clinical candidate for treatment of neurological disorders. J. Med. Chem., 2018, 61(20), 9062-9084.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00951] [PMID: 30067909]
[56]
Fabian, J.; Mergemeier, K.; Lehr, M. Evaluation of inhibitors of the arachidonic acid cascade with intact platelets using an on-line dilution and on-line solid phase extraction HPLC–MS method. Prostaglandins Other Lipid Mediat., 2021, 155, 106551.
[http://dx.doi.org/10.1016/j.prostaglandins.2021.106551] [PMID: 33940184]
[57]
Spadoni, G.; Stankov, B.; Duranti, A.; Biella, G.; Lucini, V.; Salvatori, A.; Fraschini, F. 2-Substituted 5-methoxy-N-acyltryptamines: Synthesis, binding affinity for the melatonin receptor, and evaluation of the biological activity. J. Med. Chem., 1993, 36(25), 4069-4074.
[http://dx.doi.org/10.1021/jm00077a010] [PMID: 8258829]
[58]
Di, L.; Kerns, E.H. Solubility. In: Drug-like properties: Concepts, structure design and methods from ADME to toxicity optimization, 2nd ed; Academic Press, 2016; pp. 61-92.
[http://dx.doi.org/10.1016/B978-0-12-801076-1.00007-1]
[59]
Ishikawa, M.; Hashimoto, Y. Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry. J. Med. Chem., 2011, 54(6), 1539-1554.
[http://dx.doi.org/10.1021/jm101356p] [PMID: 21344906]
[60]
Bachovchin, D.A.; Cravatt, B.F. The pharmacological landscape and therapeutic potential of serine hydrolases. Nat. Rev. Drug Discov., 2012, 11(1), 52-68.
[http://dx.doi.org/10.1038/nrd3620] [PMID: 22212679]
[61]
Brideau, C.; Kargman, S.; Liu, S.; Dallob, A.L.; Ehrich, E.W.; Rodger, I.W.; Chan, C.C. A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm. Res., 1996, 45(2), 68-74.
[http://dx.doi.org/10.1007/BF02265118] [PMID: 8907587]
[62]
Singh, P.; Kaur, J.; Kaur, H.; Kaur, A.; Bhatti, R. Synergy of physico-chemical and biological experiments for developing a cyclooxygenase-2 inhibitor. Sci. Rep., 2018, 8(1), 10005.
[http://dx.doi.org/10.1038/s41598-018-28408-8] [PMID: 29968808]
[63]
Young, J.M.; Panah, S.; Satchawatcharaphong, C.; Cheung, P.S. Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and-2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production. Inflamm. Res., 1996, 45(5), 246-253.
[http://dx.doi.org/10.1007/BF02259611] [PMID: 8737748]
[64]
Smith, C.J.; Zhang, Y.; Koboldt, C.M.; Muhammad, J.; Zweifel, B.S.; Shaffer, A.; Talley, J.J.; Masferrer, J.L.; Seibert, K.; Isakson, P.C. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc. Natl. Acad. Sci., 1998, 95(22), 13313-13318.
[http://dx.doi.org/10.1073/pnas.95.22.13313] [PMID: 9789085]
[65]
Sud’ina, G.F.; Pushkareva, M.A.; Shephard, P.; Klein, T. Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors. Prostaglandins Leukot. Essent. Fatty Acids, 2008, 78(2), 99-108.
[http://dx.doi.org/10.1016/j.plefa.2007.12.006] [PMID: 18280718]
[66]
Pommery, J.; Pommery, N.; Hénichart, J.P. Modification of eicosanoid profile in human blood treated by dual COX/LOX inhibitors. Prostaglandins Leukot. Essent. Fatty Acids, 2005, 73(6), 411-417.
[http://dx.doi.org/10.1016/j.plefa.2005.08.009] [PMID: 16213697]
[67]
Surette, M.E.; Odeimat, A.; Palmantier, R.; Marleau, S.; Poubelle, P.E.; Borgeat, P. Reverse-phase high-performance liquid chromatography analysis of arachidonic acid metabolites in plasma after stimulation of whole blood ex vivo. Anal. Biochem., 1994, 216(2), 392-400.
[http://dx.doi.org/10.1006/abio.1994.1057] [PMID: 8179194]
[68]
Frohberg, P.; Drutkowski, G.; Wobst, I. Monitoring eicosanoid biosynthesis via lipoxygenase and cyclooxygenase pathways in human whole blood by single HPLC run. J. Pharm. Biomed. Anal., 2006, 41(4), 1317-1324.
[http://dx.doi.org/10.1016/j.jpba.2006.02.046] [PMID: 16621414]
[69]
Margalit, A.; Duffin, K.L.; Isakson, P.C. Rapid quantitation of a large scope of eicosanoids in two models of inflammation: Development of an electrospray and tandem mass spectrometry method and application to biological studies. Anal. Biochem., 1996, 235(1), 73-81.
[http://dx.doi.org/10.1006/abio.1996.0093] [PMID: 8850549]
[70]
Shi, Y.; Murrey, H.E.; Ahn, K.; Weng, N.; Patel, S. LC-MS/MS assay for the simultaneous quantitation of thromboxane B2 and prostaglandin E2 to evaluate cyclooxygenase inhibition in human whole blood. J. Appl. Bioanal., 2020, 6(3), 131-144.
[http://dx.doi.org/10.17145/jab.20.014]
[71]
Oda, Y.; Mano, N.; Asakawa, N. Simultaneous determination of thromboxane B2, prostaglandin E2 and leukotriene B4 in whole blood by liquid chromatography/mass spectrometry. J. Mass Spectrom., 1995, 30(12), 1671-1678.
[http://dx.doi.org/10.1002/jms.1190301206]
[72]
Meirer, K.; Glatzel, D.; Kretschmer, S.; Wittmann, S.; Hartmann, M.; Blöcher, R.; Angioni, C.; Geisslinger, G.; Steinhilber, D.; Hofmann, B.; Fürst, R.; Proschak, E. Design, synthesis and cellular characterization of a dual inhibitor of 5-lipoxygenase and soluble epoxide hydrolase. Molecules, 2016, 22(1), 45.
[http://dx.doi.org/10.3390/molecules22010045] [PMID: 28036068]
[73]
Maier, T.J.; Tausch, L.; Hoernig, M.; Coste, O.; Schmidt, R.; Angioni, C.; Metzner, J.; Groesch, S.; Pergola, C.; Steinhilber, D.; Werz, O.; Geisslinger, G. Celecoxib inhibits 5-lipoxygenase. Biochem. Pharmacol., 2008, 76(7), 862-872.
[http://dx.doi.org/10.1016/j.bcp.2008.07.009] [PMID: 18692027]
[74]
Ghasemi, A.; Elfringhoff, A.S.; Lehr, M. Structure–activity relationship studies of 3-dodecanoylindole-2-carboxylic acid inhibitors of cytosolic phospholipase A2 α-mediated arachidonic acid release in intact platelets: Variation of the keto moiety. J. Enzyme Inhib. Med. Chem., 2005, 20(5), 429-437.
[http://dx.doi.org/10.1080/14756360500228338] [PMID: 16335050]
[75]
Janssen, G.M.E.; Venema, J.F. Ibuprofen: Plasma concentrations in man. J. Int. Med. Res., 1985, 13(1), 68-73.
[http://dx.doi.org/10.1177/030006058501300110] [PMID: 3979659]
[76]
Shen, Z.; Tieu, K.; Wilson, D.; Bucci, G.; Gillen, M.; Lee, C.; Kerr, B. Evaluation of pharmacokinetic interactions between lesinurad, a new selective urate reabsorption inhibitor, and commonly used drugs for gout treatment. Clin. Pharmacol. Drug Dev., 2017, 6(4), 377-387.
[http://dx.doi.org/10.1002/cpdd.323] [PMID: 28074640]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy