Skip to main content
SpringerLink
Log in
Book cover

Antirheumatic Therapy: Actions and Outcomes pp 1–24Cite as

Medicinal chemistry of the disease modifying anti-rheumatic drugs

  • Chapter

  • 779 Accesses

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

The disease modifying anti-rheumatic drugs (DMARD) and the corticosteroids constitute a great variety of chemical compounds and, as is the case with all drugs, the chemical properties of the DMARD and corticosteroids are important aspects of their pharmacology. In this chapter, the medicinal chemistry of the various DMARD is discussed. The coverage includes the chemical factors that affect their handling by the body. In addition to the DMARD discussed in this book, the chemistry of penicillamine is also described. Although the use of penicillamine as an anti-rheumatic drug has declined in recent years, thiol compounds, such as penicillamine, are still of great interest because of their antioxidant activity and potential activities in inflammatory states.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Warhurst DC, Steele JCP, Adagu IS, Craig JC, Cullander C (2003) Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum, in agreement with its physicochemical properties. J Antimicrob Chemother 52: 188–193

    Article  CAS  PubMed  Google Scholar 

  2. Drayton CJ (1990) Comprehensive medicinal chemistry, Volume 6. Pergamon Press, Oxford

    Google Scholar 

  3. Thummel KE, Shen DD (1996) Dosage and optimization of dosage regimens; Pharmacokinetic data. In: JG Hardman, LE Limbird (eds): The Pharmacological Basis of Therapeutics, Edition 10. McGraw-Hill, New York 1917–2023

    Google Scholar 

  4. Cutler DJ, Maclntyre AC, Tett SE (1988) Pharmacokinetics and cellular uptake of 4-aminoquinolone antimalarials. Agents Actions (Suppl) 24: 142–157

    CAS  Google Scholar 

  5. Krogstad DJ, Schlesinger PH (1986) A perspective on antimalarial action: effects of weak bases on Plasmodium falciparum. Biochem Pharmacol 35: 547–552

    Article  CAS  PubMed  Google Scholar 

  6. Fürst DE, Lindsley H, Baethge B, Botstein GR, Caldwell J, Dietz F, Ettlinger R, Golden HE, McLaughlin GE, Moreland LW et al (1999) Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension. Arthritis Rheum 42: 357–365

    Article  PubMed  Google Scholar 

  7. McLachlan AJ, Tett SE, Cutler DJ, Day RO (1993) Disposition of the enantiomers of hydroxychloroquine in patients with rheumatoid arthritis following multiple doses of the racemate. Br J Clin Pharmacol 36: 78–81

    CAS  PubMed  Google Scholar 

  8. McLachlan AJ, Cutler DJ, Tett SE (1993) Plasma protein binding of the enantiomers of hydroxyquinoline and metabolites. Eur J Clin Pharmacol 44: 481–484

    Article  CAS  PubMed  Google Scholar 

  9. Elion GB (1989) The purine path to chemotherapy. Science 244: 41–47

    Article  CAS  PubMed  Google Scholar 

  10. Weinshilboum R (2001) Thiopurine pharmacognetics: clinical and molecular studies of thiopurine methylpurine transferase. Drug Metab Disp 29: 601–605

    CAS  Google Scholar 

  11. Marra CA, Esdaile JM, Anis AH (2002) Practical pharmacogenetics: the cost effectiveness of screening for thiopurine S-transmethylase (TPMT) polymorphisms in patients with rheumatological conditions treated with azathioprine. J Rheumatol 29: 2507–2512

    PubMed  Google Scholar 

  12. Seidman EG, Fürst DE (2002) Pharmacogenetics for the individualization of treatment of rheumatological disorders using azathioprine. J Rheumatol 29: 2507–2512

    Google Scholar 

  13. Dubinsky MC, Lamothe S, Yang HY et al (2000) Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 118: 705–713

    Article  CAS  PubMed  Google Scholar 

  14. Yocum DE, Fürst DE, Kaine JL, Baldassare AR, Stevenson JT, Borton MA, Mengle-Gaw LJ, Schwatz BD, Wisemandle W, Mekki OA et al (2003) Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double blind trial. Arthritis Rheum 48: 3328–3337

    Article  CAS  PubMed  Google Scholar 

  15. Huai Q, Kim H-Y, Liu Y, Zhao Y, Mondragon A, Liu JO, Ke H (2002) Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes. Proc Nat Acad Sci USA 99: 12037–12042

    Article  CAS  PubMed  Google Scholar 

  16. Kean WF, Lock CJL, Howard-Lock HE (1991) Chirality in antirheumatic drugs. Lancet 338: 1565–1568

    Article  CAS  PubMed  Google Scholar 

  17. Gerber RC, Paulus HE, Bluestone R, Lederer M (1972) Kinetics of aurothiomalate in serum and synovial fluid Arthritis Rheum 15: 625–629

    Article  CAS  PubMed  Google Scholar 

  18. Ghadially FN (1979) Ultrastructural localization and in situ analysis of iron, bismuth and gold inclusions. CRC Crit Rev Toxicol 6: 303–350

    Article  CAS  PubMed  Google Scholar 

  19. Graham GG, Champion GD, Ziegler JB (1994) The cellular metabolism and effects of gold complexes. Metal Based Drugs 1: 395–404

    Article  CAS  PubMed  Google Scholar 

  20. Shaw CF (1999) The biochemistry of gold. In: H Schmidbaur (ed): Gold: Progress in Chemistry, Biochemistry and Technology. John Wiley, New York 259–308

    Google Scholar 

  21. Crooke ST, Snyder RM, Butt TR, Ecker DJ, Allaudeen HS, Monia B, Mirabelli CK (1986) Cellular and molecular pharmacology of auranofin and related gold complexes. Biochem Pharmacol 35: 3423–3431

    Article  CAS  PubMed  Google Scholar 

  22. Canumalla AJ, Al-Zamil N, Phillips M, Isab AA, Shaw CF (2001) Redox and ligand exchange reactions of potential gold(I) and gold(III)-cyanide metabolites under biomimetic conditions. J Inorg Biochem 85: 67–76

    Article  CAS  PubMed  Google Scholar 

  23. Rozman B (2002) Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41: 421–430

    Article  CAS  PubMed  Google Scholar 

  24. Kim HA, Song Y (1997) A comparison between bucillamine and D-penicillamine in the treatment of rheumatoid arthritis. Rheumatol Int 17: 5–9

    Article  CAS  PubMed  Google Scholar 

  25. Jaffe IA (1980) Thiol compounds with penicillamine-like activity and possible mode of action in rheumatoid arthritis. Clin Rheum Dis 6 (3), 633–645

    Google Scholar 

  26. Bird HA, Le Gallez P, Dixon JS, Catalano MA, Traficante A, Liauw LA, Sussman H, Rotman H, Wright V (1990) A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis. J Rheumatol 17: 603–608

    CAS  PubMed  Google Scholar 

  27. Jonsson H, Wollheim FA, Svensson B (1986) No effect of acetylcystein on refractory arthritis. Clin Exp Rheumatol 4: 363–364

    CAS  PubMed  Google Scholar 

  28. Kroger H, Miesel R, Dietrich A, Ohde M, Altrichter S, Braun C, Ockenfels H (1997) Suppression of type II collagen-induced arthritis by N-acetyl-L-cysteine in mice. Gen Pharmacol 29: 671–674

    Article  CAS  PubMed  Google Scholar 

  29. Harbar JA, Cusworth DC, Lawes LC, Wrong OM (1986) Comparison of 2-mercaptopropionylglycine and D-penicillamine in the treatment of cystinuria. J Urol 136: 146–149

    CAS  PubMed  Google Scholar 

  30. Munday R (1989) Toxicity of thiols and disulphides: involvement of free-radical species. Free Rad Biol Med 7: 659–673

    Article  CAS  PubMed  Google Scholar 

  31. Svartz N (1942) Salazopyrin, a new sulfanilamide preparation: a. therapeutic results in rheumatic polyarthritis; b. therapeutic results in ulcerative colitis; c. toxic manifestations in treatment with sulfanilamide preparations. Acta Med Scand 110: 577–598

    Google Scholar 

  32. Bondesen S, Nielsen OH, Schou JB, Jensen PH, Lassen LB, Binder V, Krasilnikoff PA, Dano P, Hansen SH, Jacobsen O et al (1986) Steady-state kinetics of 5-aminosalicylic acid and sulphapyridine during sulfasalazine prophylaxis in ulcerative colitis. Scand J Gastroenterol 21: 693–700

    Article  CAS  PubMed  Google Scholar 

  33. Taggart AJ, McDermott BJ, Roberts SD (1992) The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis. Clin Pharmacokin 23: 311–320

    Article  CAS  Google Scholar 

  34. Pullar T, Hunter JA, Capell HA (1985) Which component of sulphasalazine is active in rheumatoid arthritis. Br Med J 290: 1535–1538

    Article  CAS  Google Scholar 

  35. Astbury C, Hill J, Bird HA (1988) Co-trimoxazole in rheumatoid arthritis: a comparison with sulphapyridine. Ann Rheum Dis 47: 323–327

    Article  CAS  PubMed  Google Scholar 

  36. Chapman CM, Zwillich SH (1994) Olsalazine in ankylosing spondylitis: a pilot study. J Rheumatol 21: 1699–1701

    CAS  PubMed  Google Scholar 

  37. Gringauz A (1997) Medicinal Chemistry. Wiley-VCH, New York

    Google Scholar 

  38. Saivin S, Houin G (1988) Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokin 15: 355–366

    Article  CAS  Google Scholar 

  39. Endou H (2002) Human anion transporters mediate the transport of teracycline. Jap J Pharmacol 88: 69–76

    Article  PubMed  Google Scholar 

  40. Leydon JJ (1985) Absorption of minocycline hydrochloride and tetracycline. Effect of food, milk, and iron. J Am Acad Dermatol 12: 308–312

    Article  Google Scholar 

  41. Zeelen FJ (1990) Medicinal chemistry of steroids. Elsevier, Amsterdam

    Google Scholar 

  42. Toutain PL, Alvinerie M, Fayolle P, Ruckebusch Y (1986) Bovine plasma and synovial fluid kinetics of methylprednisolone and methylprednisolone acetate after intraarticular administration of methylprednisolone acetate. J Pharmacol Exp Ther 236: 794–802

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia

    Garry G. Graham

  2. Department of Clinical Pharmacology, St Vincent’s Hospital, Sydney, NSW, 2010, Australia

    Garry G. Graham

Authors
  1. Garry G. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Clinical Pharmacology and Toxicology, St. Vincent’s Hospital Sydney, Victoria Street Darlinghurst, Sydney, NSW, 2010, Australia

    Richard O. Day

  2. 546 Dept. of Rheumatology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Piet L. C. M. van Riel

  3. Carl M.Pearson Professor of Rheumatology, 1000 Veteran Ave Rm 32-59, Los Angeles, CA, 90025-1670, USA

    Daniel E. Fürst

  4. Department of Rheumatology, St Vicent’s University Hospital, Elm Park, Dublin 4, Ireland

    Barry Bresnihan

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Graham, G.G. (2005). Medicinal chemistry of the disease modifying anti-rheumatic drugs. In: Day, R.O., Fürst, D.E., van Riel, P.L.C.M., Bresnihan, B. (eds) Antirheumatic Therapy: Actions and Outcomes. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7726-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-7643-7726-7_1

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-6595-0

  • Online ISBN: 978-3-7643-7726-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation