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Cited by 644Analytical Chemistry and ChromatographyChemistry and Stereochemistry StudiesAsymmetric Synthesis and Catalysis

The DOI matches its Crossref record; 77 of the 100 references it cites were found in a registry or an index.

Putting chirality to work: the strategy of chiral switches

Agranat, Israel, Caner, Hava, Caldwell, John·2002·Nature Reviews Drug Discovery
DOI 10.1038/nrd915
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Abstract

Most of the new drugs reaching the market today are single enantiomers, rather than the racemic mixtures that dominated up to ten years ago. Many of the new single-enantiomer drugs were developed as such, but there are also important examples of new single-enantiomer drugs derived from 'chiral switches' of established racemates. Indeed, a well-timed chiral switch can offer enhanced therapy and further profitability as a 'line extension' of a major racemic drug with patents that are expiring.

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23 of the 100 references couldn’t be matched to a known paper.

Research works printed but not linked: 50

  1. Aboul-Enein, H. Y. & Wainer, I. W. (eds) The Impact of Stereochemistry on Drug Development and Use (Chemical Analysis Vol. 142) (Wiley, New York, 1997).
  2. Caldwell, J. Through the looking glass in chiral drug development. Modern Drug Discov. 2, 51–60 (1999).A review of the opportunities for chiral drugs and the global regulatory environment that influences their development.
  3. Challener, C. A. (ed.) Chiral Drugs (Ashgate, Burlington, Vermont, 2001).
  4. Eichelbaum, M., Testa, B. & Somogyi, A. (eds) Stereochemical Aspects of Drug Action (Springer, Heidelberg, 2002).
  5. Blumenstein, J. J. in Chirality in Industry II: Development in the Commercial Manufacture and Application of Optically Active Compounds (eds Collins, A. N., Sheldrake, G. N. & Crosby, J.) 11–18 (Wiley, New York, 1997).
  6. Agranat, I. & Sarel, S. Introduction. Reflections on chiral discrimination. Enantiomer 1, 249–250 (1996).
  7. Bristol, J. A. & Doherty, A. M. (eds) To Market, To Market in Annual Reports in Medicinal Chemistry Vols 25–36 (Academic Press, San Diego, California, 1990–2001).
  8. Miller, S. P. FDA perspectives on quality control for chiral pharmaceuticals. 13th Int. Symp. Chiral Discrimination Abstract L/316 and lecture (2001).
  9. Branch, S. K. Regulatory issues and validation in chiral analysis. The Chiral Technology Conference 2000, CPI Worldwide, Milano (2000).
  10. Gal, J. & Agranat, I. Comments Submitted to the US Food and Drug Administration (FDA) in response to FDA Notice on Policy Period of Marketing Exclusivity for Newly Approved Drug Products With Enantiomer Active Ingredients 62 Fed. Reg. 2167 FDA Dkt No. 97N-0002, Comment No. 7327 (1997).
  11. Handley, D. A. The therapeutic advantages achieved through single-isomer drugs. Pharm. News 6, 11–15 (1999).
  12. Cannarsa, M. J. Racemic switches: historical perspectives and current status. Chem. Oggi/Chem. Today 17, 28–32 (1999).
  13. Department of Health and Human Services. The International Conference on Harmonization; guidance on Q6A specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. US Food and Drug Administration 〈 http://www.fda.gov/cber/gdlns/frich122900.pdf 〉 (2000).
  14. US Food and Drug Administration. FDA Staff Manual Guide 4820.3. Drug Classification and Priority Review Policy (US Food and Drug Administration, 1992).
  15. Carlson, S. C. The case against market exclusivity for purified enantiomers of approved drugs. Yale Symp. Law Technol. Vol. 6 (1999).
  16. Nayler, J. H. C. & Long, A. A. W. P-hydroxyampicillin and salts thereof. GB Patent 1,214,844 (1972).
  17. Nayler, J. H. C. & Simth, H. Penicillins. GB Patent 978,178 (1964).
  18. Hoogerwerf, W. A. & Pastricha, P. J. in Goodman and Gilman'sThe Pharmacological Basis of Therapeutics 10th edn (eds Hardman, J. G., Limbird, L. E. & Gilman, A. G.) 1005–1029 (McGraw Hill, New York, 2002).
  19. Wong, P. Gastrointestinal Disorders: New Therapies for the New Millenium (PJB Publications, New York, 2000).A guide to gastrointestinal disorders and their treatments, including gastric antisecretory PPI drugs, such as omeprazole and esomeprazole.
  20. Lindberg, P. & Weidoff, L. Method for the treatment of gastric acid-related diseases and production of medication using (−)-enantiomer of omeprazole. US Patent 5,877,192 (1999).
  21. Lindberg, P. & von Unge, S. Compositions. US Patent 5,714,504 (1998).
  22. Graham, D., Holt, R., Taylor, S. & Lindberg, P. Method for preparing a pharmaceutically active enantiomeric or enantiomerically enriched sulfoxide compound by enantioselective bioreduction of a racemate sulfoxide compound. US Patent 5,776,765 (1998).
  23. von Unge, S. Process for preparing pure salts of pyridinylmethyl-sulfinyl-1H-benzimidazole. US Patent 5,693,818 (1997).
  24. Kohl, B. D. & Senn-Bilfinger, J. D. Enantiomerentrennung. DE Patent 4,035,455 (1992).
  25. Jenkins, D. J., Sancilio, F. D., Stowell, G. W., Whittall, L. B. & Whittle, R. R. Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same. US Patent 6,262,085 (2001).
  26. Fontana, S. A. et al. Pharmaceutical unit dosage form. US Patent 6,262,086 (2001).
  27. Fontana, S. A. et al. Dry blend pharmaceutical formulations. US Patent 6,268,385 (2001).
  28. Jenkins, D. J., Sancilio, F. D., Stowell, G. W., Whittall, L. B. & Whittle, R. R. Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same. US Patent 6,369,087 (2002).
  29. Jenkins, D. J. et al. Method of improving bioavailability. US Patent 6,312,712 (2001).
  30. Fontana, S. A. et al. Pharmaceutical unit dosage form. US Patent 6,312,723 (2001).
  31. Jenkins, D. J. et al. Pharmaceutical formulations. US Patent 6,316,020 (2001).
  32. Fontana, S. A. et al. Dry blend pharmaceutical unit dosage form. US Patent 6,326,384 (2001).
  33. Nicolaidis, S. (ed.) Obesity Management of Redux™ (Academic, San Diego, California, 1997).
  34. Wurtman, R. J. & Wurtman, J. J. d-Fenfluramine for modifying feeding behavior. US Patent 4,309,445 (1982).
  35. Wurtman, R. J. & Wurtman, J. J. Method of utilizing d,l-fenfluramine for modifying feeding behavior. US Patent 4,452,815 (1984).
  36. Anonymous. Redux slated for US patent extension. SCRIP 2191, 19 (1996).
  37. Young, J. W. & Barberich, T. J. Method for treating migraine headaches using optically pure S-(+)-fluoxetine. US patent 5,589,511 (1996).
  38. Young, J. W., Barberich, T. J. & Teicher, M. H. Methods for treating depression and other disorders using optically pure R-(−)-fluoxetine and monoamine oxidase inhibitor. US patent 5,648,396 (1997).
  39. Fuller, R. W., Robertson, D. W. & Wong, D. T. (S)-Norfluoxetine in method of inhibiting serotonin uptake. US patent 5,250,571 (1993).
  40. Robertson, D. W. & Wong, D. T. (R)-Norfluoxetine in method for occupying serotonin IC receptors. US patent 5,250,572 (1993).
  41. Anonymous. Lilly Sepracor deal on R-fluoxetine. SCRIP 2395, 8 (1998).
  42. Schmiegel, K. K. & Molloy, B. B. Treatment of obesity with aryloxyphenylpropylamines. US patent 4,626,549 (1986).
  43. Schmiegel, K. K. & Molloy, B. B. Aryloxyphenylpropylamines in treating depression. US patent 4,018,895 (1977).
  44. Schmiegel, K. K. & Molloy, B. B. Arloxyphenylpropylamines. US patent 4,314,081 (1982).
  45. Stark, P. Anti-anxiety method. US patent 4,590,213 (1986).
  46. Rogers, R. S. Sepracor: skating on 'ICE'. Chem. Eng. News 76, 11–13 (1998).
  47. Roden, D. in Goodman and Gilman's The Pharmacological Basis of Therapeutics 10th edn (Hardman, J. G., Limbird, L. E. & Gilman, A. G.) 933–970 (McGraw Hill, New York, 2002).
  48. Toft, A. S. & Bogeso, K. P. Anti-depressive substituted 1-dimethylaminopropyl-1-phenyl phthalans. US Patent 4,136,193 (1979).
  49. Toft, A. S. & Bogeso, K. P. Anti-depressive substituted 1-dimethylaminopropyl-1-phenyl phthalans. GB Patent 1,526,331 (1979).
  50. Braestrup, C. in Optimising the Treatment of Mood and Anxiety Disorders 13–17 (Lundbeck, Copenhagen, 2002).

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Metadata

Authors
Agranat, I., Caner, H., & Caldwell, J.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Imperial College London (GB)
Corresponding author
Agranat, Israel
ORCID
Venue
Nature Reviews Drug Discovery
Publisher
Springer Science and Business Media LLC
Published
2002-10
Volume
1
Issue
10
Pages
753-768
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
DOI
10.1038/nrd915
OpenAlex
W1991998089
Cited by
637
References
100
Citations by year
2026: 32 · 2025: 31 · 2024: 43 · 2023: 29 · 2022: 31 · 2021: 36 · 2020: 33 · 2019: 32 · 2018: 32 · 2017: 31 · 2016: 15 · 2015: 31 · 2014: 25 · 2013: 22 · 2012: 32
FWCI
1.67
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Chemistry and Chromatography
  • Physical Sciences › Chemistry › Organic Chemistry › Chemistry and Stereochemistry Studies
  • Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
Keywords
chiral switch, racemic drugs, enantiomers, drug development strategy, line extension, patent expiry, pharmaceutical patents
MeSH terms
Animals, Chemistry, Pharmaceutical, Humans, Stereoisomerism, Technology, Pharmaceutical

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