Recent Advances in the Structural Modification of Ibuprofen

LUO Xiao, ZHU Yuchao, HUO Tongyu, JIAO Ning*

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主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
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Chinese Journal of Pharmaceuticals ›› 2018, Vol. 49 ›› Issue (06) : 707. DOI: 10.16522/j.cnki.cjph.2018.06.001
Perspectives & Review

Recent Advances in the Structural Modification of Ibuprofen

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Abstract

Ibuprofen is one of the most widely used NSAIDs in clinical, and it has a history of over 50 years for use. In order to obtain more active compounds or to reduce ibuprofen’s adverse reactions, structural modifications of ibuprofen have been developed in recent years. In this review, various studies in structural modifications of ibuprofen are summarized according to different strategies, and some recent organic synthetic methodologies are also introduced to provide a reference for the development of modification.

Key words

ibuprofen / structural modification / drug discovery / drug synthesis

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LUO Xiao, ZHU Yuchao, HUO Tongyu, JIAO Ning*. Recent Advances in the Structural Modification of Ibuprofen. Chinese Journal of Pharmaceuticals. 2018, 49(06): 707 https://doi.org/10.16522/j.cnki.cjph.2018.06.001

References

[1] Rainsford KD. Ibuprofen: from invention to an OTC therapeutic mainstay [J]. Int J Clin Pract, 2013, 67(s178):9-20.
[2] McGeer PL, McGeer EG. NSAIDs and Alzheimer disease:epidemiological, animal model and clinical studies [J].Neurobiol Aging, 2007, 28(5): 639-647.
[3] Weggen S, Rogers M, Eriksen J. NSAIDs: small molecules for prevention of Alzheimer's disease or precursors for future drug development? [J]. Neurobiol Aging, 2007, 28(10):536-543.
[4] Ait Ouakrim D, Dashti SG, Chau R, et al. Aspirin, ibuprofen,and the risk for colorectal cancer in Lynch syndrome [J]. J Natl Cancer Inst, 2016, 108(2): djv384.
[5] Janakiram NB, Mohammed A, Lang ML, et al. Immune modulation by agents used in the prevntion and treatment of colon and pancreatic cancers. in cancer immunology [M].Berlin: Springer Berlin Heidelberg, 2015: 249-275.
[6] Chandrasekharan NV, Dai H, Roos KLT, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression [J]. Proc Natl Acad Sci USA, 2002, 99(21):13926-13931.
[7] Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclooxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis [J]. Proc Natl Acad Sci USA,1999, 96(13): 7563-7568.
[8] Flower RJ. The development of COX2 inhibitors [J]. Nat Rev Drug Discov, 2003, 2(3): 179-191.
[9] Buttgereit F, Burmester GR, Simon LS. Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors [J]. Am J Med, 2001,110(3): 13-19.
[10] Wallace JL. Selective COX-2 inhibitors: is the water becoming muddy? [J]. Neurobiol Aging, 1999, 20(1): 4-6.
[11] Nichol KJ, Allen DW. The medicinal chemistry of ibuprofen.in. Ibuprofen: Discovery, development and therapeutics [M].New York: John Wiley & Sons Ltd., 2015: 22-50.
[12] Mittal S, Malde A, Selvam C, et al. Synthesis and evaluation of S-4-(3-thienyl)phenyl-α-methylacetic acid [J]. Bioorg Med Chem Lett, 2004, 14(4): 979-982.
[13] 郭长彬, 陈晓红, 易 翔, 等. 布洛芬衍生物的合成及抗炎镇痛活性[J]. 化学学报, 2005, 63(9): 841-848.
[14] Sujith KV, Rao JN, Shetty P, et al. Regioselective reaction:synthesis and pharmacological study of Mannich bases containing ibuprofen moiety [J]. Eur J Med Chem, 2009,44(9): 3697-3702.
[15] Maxwell JR, Wasdahl DA, Wolfson AC, et al. Synthesis of 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and [(4-phenyl-5-aryl-4H-1,2,4-triazol-3-yl)thio]acetic acids as possible superoxide scavengers and antiinflammatory agents [J]. J Med Chem, 1984, 27(12): 1565-1570.
[16] Ashok M, Holla BS, Poojary B. Convenient one pot synthesis and antimicrobial evaluation of some new Mannich bases carrying 4-methylthiobenzyl moiety [J]. Eur J Med Chem,2007, 42(8): 1095-1101.
[17] Uzg?ren-Baran A, Tel BC, Sar?g?l D, et al. Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen:novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance [J]. Eur J Med Chem, 2012, 57:398-406.
[18] Bansal Y, Kaur M, Silakari O. Benzimidazole-ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases [J]. Eur J Med Chem, 2015, 89: 671-682.
[19] Lassalas P, Oukoloff K, Makani V, et al. Evaluation of oxetan-3-ol, thietan-3-ol, and derivatives thereof as bioisosteres of the carboxylic acid functional group [J]. ACS Med Chem Lett, 2017, 8(8): 864-868.
[20] Khan MS, Akhter M. Synthesis, pharmacological activity and hydrolytic behavior of glyceride prodrugs of ibuprofen [J].Eur J Med Chem, 2005, 40(4): 371-376.
[21] Katritzky AR, Jishkariani D, Narindoshvili T. Convenient synthesis of ibuprofen and naproxen aminoacyl, dipeptidoyl and ester derivatives [J]. Chem Biol Drug Des, 2009, 73(6):618-626.
[22] Zhao X, Chen D, Gao P, et al. Synthesis of ibuprofen eugenol ester and its microemulsion formulation for parenteral delivery [J]. Chem Pharm Bull, 2005, 53(10): 1246-1250.
[23] Uhrig RK, Picard MA, Beyreuther K, et al. Synthesis of antioxidative and anti-inflammatory drugs glucoconjugates[J]. Carbohydr Res, 2000, 325(1): 72-80.
[24] Zhao X, Tao X, Wei D, et al. Pharmacological activity and hydrolysis behavior of novel ibuprofen glucopyranoside conjugates [J]. Eur J Med Chem, 2006, 41(11): 1352-1358.
[25] Chen Q, Gong T, Liu J, et al. Synthesis, in vitro and in vivo characterization of glycosyl derivatives of ibuprofen as novel prodrugs for brain drug delivery [J]. J Drug Target, 2009,17(4): 318-328.
[26] Duan Y, Yu J, Liu S, et al. Synthesis of anthraquinoneibuprofen prodrugs with hydroxyapatite affinity and anti-inflammatory activity characteristics [J]. Med Chem, 2009,5(6): 577-582.
[27] Zhao Y, Qu B, Wu X, et al. Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with “lock-in” function [J]. Eur J Med Chem,2014, 82: 314-323.
[28] Xin G, Wang Y, Guo X, et al. Synthesis of diosgeninibuprofen derivatives and their activities against insulindependent diabetes mellitus [J]. Chem Pharm Bull, 2013,61(5): 532-538.
[29] Banekovich C, Ott I, Koch T, et al. Synthesis and biological activities of novel dexibuprofen tetraacetylriboflavin conjugates [J]. Bioorg Med Chem Lett, 2007, 17(3): 683-687.
[30] Theodosis-Nobelos P, Tziona P, Poptsis A, et al. Novel polyfunctional esters of ibuprofen and ketoprofen with hypolipidemic, lipoxygenase inhibitory and enhanced anti-inflammatory activity [J]. Med Chem Res, 2017, 26(2): 461-472.
[31] Saeed A, Channar PA, Larik FA, et al. Design, synthesis,molecular docking studies of organotin-drug derivatives as multi-target agents against antibacterial, antifungal,α-amylase, α-glucosidase and butyrylcholinesterase [J].Inorg Chim Acta, 2017, 464: 204-213.
[32] Ingram MJ, Moynihan HA, Powell MW, et al. Synthesis and hydrolytic behaviour of glycerol-1,2-diibuprofenate-3-nitrate, a putative pro-drug of ibuprofen and glycerol-1-nitrate [J]. J Pharm Pharmacol, 2001, 53(3): 345-350.
[33] Sarkate AP, Lokwani DK, Patil AA, et al. Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenicity and nitric oxide-releasing studies of novel ibuprofen analogs as nonulcerogenic derivatives [J]. Med Chem Res, 2011,20(7): 795-808.
[34] Borhade N, Pathan AR, Halder S, et al. NO-NSAIDs. Part 3: nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs [J]. Chem Pharm Bull(Tokyo), 2012,60(4): 465-481.
[35] Lolli ML, Cena C, Medana C, et al. A new class of ibuprofen derivatives with reduced gastrotoxicity [J]. J Med Chem,2001, 44(21): 3463-3468.
[36] Velázquez C, Praveen Rao PN, Knaus EE. Novel nonsteroidal antiinflammatory drugs possessing a nitric oxide donor diazen-1-ium-1,2-diolate moiety: design, synthesis, biological evaluation, and nitric oxide release studies [J]. J Med Chem,2005, 48(12): 4061-4067.
[37] Velázquez CA, Praveen Rao NP, Citro ML, et al. O2-Acetoxymethyl-protected diazeniumdiolate-based NSAIDs(NONO-NSAIDs): Synthesis, nitric oxide release, and biological evaluation studies [J]. Bioorg Med Chem, 2007,15(14): 4767-4774.
[38] Huang Z, Velázquez CA, Abdellatif KRA, et al.Ethanesulfohydroxamic acid ester prodrugs of nonsteroidal anti-inflammatory drugs(NSAIDs): synthesis, nitric oxide and nitroxyl release, cyclooxygenase inhibition, antiinflammatory,and ulcerogenicity index studies [J]. J Med Chem, 2011, 54(5): 1356-1364.
[39] Cocco MT, Congiu C, Onnis V, et al. Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties [J]. Eur J Med Chem, 2003, 38(5):513-518.
[40] Ahmadi A, Khalili M, Olama Z, et al. Synthesis and study of analgesic and anti-inflammatory activities of amide derivatives of ibuprofen [J]. Mini-Rev Med Chem, 2017,17(9): 799-804.
[41] Chatterjee NR, Kulkarni AA, Ghulekar SP. Synthesis,pharmacological activity and hydrolytic behavior of ethylenediamine and benzathine conjugates of ibuprofen [J].Eur J Med Chem, 2008, 43(12): 2819-2823.
[42] Siskou IC, Rekka EA, Kourounakis AP, et al. Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties [J]. Bioorg Med Chem, 2007, 15(2): 951-961.
[43] Gundogdu-Hizliates C, Alyuruk H, Gocmenturk M, et al.Synthesis of new ibuprofen derivatives with their in silico and in vitro cyclooxygenase-2 inhibitions [J]. Bioorg Chem,2014, 52(2): 8-15.
[44] Al-Mekhlafi S, Alkadi H, El-Sayed MIK. Synthesis and anti-inflammatory activity of novel ketoprofen and ibuprofen derivatives [J]. J Chem Pharm Res, 2015, 7: 503-510.
[45] Bua S, Di CML, Vullo D, et al. Design and synthesis of novel nonsteroidal anti-inflammatory drugs and carbonic anhydrase inhibitors hybrids(NSAIDs-CAIs) for the treatment of rheumatoid arthritis [J]. J Med Chem, 2017, 60(3): 1159-1170.
[46] Davaran S, Entezami AA. Acrylic type polymers containing ibuprofen and indomethacin with difunctional spacer group:synthesis and hydrolysis [J]. J Controlled Release, 1997,47(1): 41-49.
[47] Babazadeh M. Synthesis and study of controlled release of ibuprofen from the new acrylic type polymers [J]. Int J Pharm, 2006, 316(1): 68-73.
[48] Cai X, Wang N, Lin X. Chemo-enzymatic synthesis of optically active polymeric prodrug of naproxen, ketoprofen and ibuprofen [J]. Polymer, 2006, 47(19): 6491-6495.
[49] Davaran S, Rashidi MR, Hanaee J, et al. Synthesis and hydrolytic behavior of ibuprofen prodrugs and their PEGylated derivatives [J]. Drug deliv, 2006, 13(5): 383-387.
[50] París R, García JM, Quijada-Garrido I. Synthesis and characterization of a new acrylic polymeric ibuprofen prodrug [J]. J Appl Polym Sci, 2010, 117(6): 3271-3276.
[51] Babazadeh M. Design, synthesis and in vitro evaluation of vinyl ether type polymeric prodrugs of ibuprofen, ketoprofen and naproxen [J]. Int J Pharm, 2008, 356(1): 167-173.
[52] Kurz M, Scriba GK. Drug-phospholipid conjugates as potential prodrugs: synthesis, characterization, and degradation by pancreatic phospholipase A2 [J]. Chem Phys Lipids, 2000, 107(2): 143-157.
[53] Xie G, Sun Y, Nie T, et al. Phospho-ibuprofen(MDC-917) is a novel agent against colon cancer: efficacy, metabolism, and pharmacokinetics in mouse models [J]. J Pharmacol Exp Ther, 2011, 337(3): 876-886.
[54] Huang L, Mackenzie GG, Ouyang N, et al. The novel phospho-non-steroidal anti-inflammatory drugs, OXT-328,MDC-22 and MDC-917, inhibit adjuvant-induced arthritis in rats [J]. Br J Pharmacol, 2011, 162(7): 1521-1533.
[55] Wong CC, Cheng KW, Xie G, et al. Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs:relevance to their pharmacological activity [J]. J Pharmacol Exp Ther, 2012, 340(2): 422-432.
[56] Nie T, Wong CC, Alston N, et al. Phospho-ibuprofen (MDC-917) incorporated in nanocarriers: anti-cancer activity in vitro and in vivo [J]. Br J Pharmacol, 2012, 166(3): 991-1001.
[57] Mattheolabakis G, Nie T, Constantinides PP, et al. Sterically stabilized liposomes incorporating the novel anticancer agent phospho-ibuprofen (MDC-917): preparation,characterization, and in vitro/in vivo evaluation [J]. PharmRes, 2012, 29(6): 1435-1443.
[58] 程 铃, 钱 珊, 樊 维, 等. 布洛芬—偕二膦酸偶联物的合成及体外靶向性研究[J]. 四川大学学报(自然科学版),2011, 48(4): 891-894.
[59] Bikzhanova GA, Toulokhonova IS, Gately S, et al. Novel silicon-containing drugs derived from the indomethacin scaffold: Synthesis, characterization and evaluation of biological activity [J]. Silicon Chem, 2007, 3(3-4): 209-217.
[60] Pérez DJ, Díaz-Reval MI, Obledo-Benicio F, et al. Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study [J].Eur J Pharmacol, 2017, 814: 18-27.
[61] Pérez DJ, Zakai UI, Guo S, et al. Synthesis and biological screening of silicon-containing ibuprofen derivatives: a study of their NF-kβ inhibitory activity, cytotoxicity, and their ability to bind IKKβ [J]. Aust J Chem, 2015, 69(6): 662-671.
[62] Song F, Salter R, Chen L. Development of decarboxylative cyanation Reactions for C-13/C-14 carboxylic acid labeling using an electrophilic cyanating reagent [J]. J Org Chem,2017, 82(7): 3530-3537.
[63] Capaldo L, Buzzetti L, Merli D, et al. Smooth photocatalyzed benzylation of electrophilic olefins via decarboxylation of arylacetic acids [J]. J Org Chem, 2016, 81(16): 7102-7109.
[64] Lang SB, Cartwright KC, Welter RS, et al. Photocatalytic aminodecarboxylation of carboxylic acids [J]. European J Org Chem, 2016, 2016(20): 3331-3334.
[65] Huang X, Liu W, Hooker JM, et al. Targeted fluorination with the fluoride ion by manganese-catalyzed decarboxylation [J].Angew Chem Int Ed Engl, 2015, 54(17): 5241-5245.
[66] McNeill E, Du Bois J. Catalytic C-H oxidation by a triazamacrocyclic ruthenium complex [J]. Chem Sci, 2012,3(6): 1810-1813.
[67] Liang YF, Jiao N. Highly efficient C-H hydroxylation of carbonyl compounds with oxygen under mild conditions [J].Angew Chem Int Ed Engl, 2014, 126(2): 558-562.
[68] Nagib DA, MacMillan DWC. Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis [J].Nature, 2011, 480(7376): 224-228.
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