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Synthesis of deuterium-labeled celecoxib and its metabolites

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Abstract

Celecoxib are COX2 inhibitors approved to reduce the COX2 level. Celecoxib and its major metabolites labeled with deuteriums are applied for drug metabolism studies. [2H4] celecoxib was prepared from [2H4] 4-acetamidobenzenesolfonyl through amination, hydrosis, diazotization, reduction and cyclization. After bromination and hydrolysis reaction, [2H4] hydroxy celecoxib was obtained and further oxidized by tetrabutylammonium permanganate to afford [2H4] celecoxib carboxylic acid. The title compounds showed remarkable chemical purity and isotope abundance which can be utilized in pharmacokinetic research.

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References

  1. Simmons DL, Botting RM, Hla T (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56:387–437

    Article  CAS  PubMed  Google Scholar 

  2. O’Banion MK, Sadowski HB, Winn V, Young DA (1991) A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 266(34):23261–23267

    Article  PubMed  Google Scholar 

  3. Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266(20):12866–12872

    Article  CAS  PubMed  Google Scholar 

  4. Goldstien JL, Silverstein FE, Agrawal NM et al (2000) Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 95(6):1681–1690

    Article  Google Scholar 

  5. Vane JR, Bakhe YS, Botting RM (1998) CYCLOOXYGENASES 1 and 2. Ann Rev Pharmacol Toxicol 38:97–120

    Article  CAS  Google Scholar 

  6. Chandrasekharan NV, Dai H, Roos KLT et al (2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drug: cloning, structure, and expression. Proc Natl Acad Sci USA 99(21):13926–13931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Graul A, Martel AM, Castañer J (1997) Celecoxib. Drugs Fut 22:711–714

    Article  CAS  Google Scholar 

  8. Davies NM, McLachlan AJ, Day RO, Williams KM (2000) Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 38:225–242

    Article  CAS  PubMed  Google Scholar 

  9. Paulson SK, Hribar JD, Liu NW et al (2000) Metabolism and excretion of [14C] celecoxib in healthy male volunteers. Drug Metab Dispos 28:308–314

    CAS  PubMed  Google Scholar 

  10. Tang C, Shou M, Mei Q, Rushmore TH, Rodrigues AD (2000) Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther 293:453–459

    CAS  PubMed  Google Scholar 

  11. Sandberg M, Yasar U, Strömberg P, Höög JO, Eliasson E (2002) Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br J Clin Pharmacol 54:423–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Talley JJ, Penning TD, Collins PW, et al (1995) Substituted pyrazolyl benzenesulfonamides. US5466823

  13. O′ Shea P, Tillyer RD, Wang X, et al (2000) Synthesis of 4-[5-substituted or unsubstituted phenyl)-3-substituted-1H-pyrazol-1-yl]benzenesulfonamides. US6150534

  14. Penning TD, Talley JJ, Bertenshaw SR et al (1997) Synthesis andbiological evaluation of the 1,5-diarylpyrazole class of cy-clooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene-sulfonamide. J Med Chem 40(9):1347–1365

    Article  CAS  PubMed  Google Scholar 

  15. Reddy M, Ramana V, Bell SC (2003) Process for the preparation of 1, 5-diarylpyrazoles. WO03024400A2

  16. Reddy AR, Sampath A, Goverdhan G et al (2009) A improved and scalable process for celecoxib: a selective cyclooxyagenase-2 inhibitor. Org Process Res 12(13):98–101

    Article  Google Scholar 

  17. Lynette MOH (2006) Synthesis of celecoxib via 1, 3-dipolar cycloaddition. Tetrahedron Lett 47:7943–7946

    Article  Google Scholar 

  18. Steven MG, Reuben M, Nigel AS (2011) A novel three-step synthesis of celecoxib via palladium-catalyzed direct arylation. Tetrahedron Lett 52:6000–6002

    Article  Google Scholar 

  19. Abdellatif KRA, Chowdhury MA, Dong Y et al (2008) Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its methanesulfonyl analog: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem 16(14):9694–9698

    Article  CAS  PubMed  Google Scholar 

  20. Takashima-Hirano M, Takashima T, Katayama Y et al (2011) Efficient sequential synthesis of PET Probes of the COX-2 inhibitor [11C]celecoxib and its major metabolite [11C]SC-62807 and in vivo PET evaluation. Bioorg Med Chem 19(9):2997–3004

    Article  CAS  PubMed  Google Scholar 

  21. Shi L, Li C, Chen R et al (2010) Synthesis of deuterium-labelled fosamprenavir calcium. J Labelled Com Radiopharm 53(3):147–151

    Article  CAS  Google Scholar 

  22. Chen LQ, Li J, Shen YZ (2009) Preparation of losartan 5-carboxylic acid and use thereof, US20090885A1

  23. He M, Li J, Tian L (2019) Synthesis of deuterium-labeled (3R, 5S)-fluvastatin and (3S, 5R)-fluvastatin. J Radioanal Nucl Chem 319:263–269

    Article  CAS  Google Scholar 

  24. Prabhakaran J, Majo JV, Simpson RN et al (2005) Synthesis of [11C] celecoxib: a potential PET probe for imaging COX-2 expression. J Label Compd Radiopharm 48:887–895

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the CNPC Research Institutes Safety & Environmental Technology Programme (Grant No. 2021DJ6605), National Natural Science Foundation of China (Grant No. 41472124), PetroChina Innovation Foundation (Grant Nos. 2015D-5006-0210 and 2016D-5007-0702) and Nature Science Foundation of Hubei Province (Grant No. 2016CFB178).

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Authors and Affiliations

  1. Hubei Key Laboratory of Petroleum Geochemistry and Environment, Yangtze University, 1 Daxue Road, Caidian District, Wuhan, 430100, Hubei, People’s Republic of China

    Mei He, Geng Xiang & JuLong Li

  2. Hubei Key Laboratory of Drilling and Production Engineering for Oil and Gas, Yangtze University, 1 Daxue Road, Caidian District, Wuhan, 430100, Hubei, People’s Republic of China

    Longqiang Duan & Lei Tian

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  1. Mei He
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  2. Geng Xiang
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Correspondence to Lei Tian.

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He, M., Xiang, G., Duan, L. et al. Synthesis of deuterium-labeled celecoxib and its metabolites. J Radioanal Nucl Chem 332, 5045–5050 (2023). https://doi.org/10.1007/s10967-023-09242-3

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  • DOI: https://doi.org/10.1007/s10967-023-09242-3

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