30DEC

Libyan International Conference for Health Sciences

The First Libyan International Conference for Health Sciences (2024): Open University, Tripoli, Libya
Mediterranean Journal of Pharmacy and Pharmaceutical Sciences
https://ppj.org.ly/article/doi/10.5281/zenodo.10698581

Mediterranean Journal of Pharmacy and Pharmaceutical Sciences

Review

A collective review of the synthetic approaches disclosed in prior patents to synthesize the renowned drug, Lamotrigine

Sanjay Sukumar Saralaya, Shridhara Kanakamajalu, Shashikumar Somashekar Hiriyalu

Downloads: 0
Views: 301

Abstract

In this review work, we have extracted the essential details from prior patents about the synthesis of popular drug Lamotrigine. This initiative will provide a platform for the global researchers to invent new or innovate over the existing synthetic routes to isolate Lamotrigine with good yield and purity. The details of patents were sourced from “Google patents” search tool and the process specific details were elaborated with reaction schemes. In this context, twenty-four reactions schemes were tabulated for the better understanding of the disclosed ventures. The entire chronological exfoliation of details on the synthesis of Lamotrigine provides a clear evolutional vision of its synthetic flourish towards drug commercialization.

Keywords

Lamotrigine, synthesis, cyanation, condensation, cyclization, recrystallization

References

  1. Brodie MJ, Richens A, Yuen AWC, UK Lamotrigine/Carbamazepine monotherapy trial group (1995) Double-blind comparison of Lamotrigine and Carbamazepine in newly diagnosed epilepsy. Lancet. 345 (8948): 476-479.  doi: 10.1016/s0140-6736(95)90581-2
  2. Fitton A, Goa KL (1995) Lamotrigine: An update of its pharmacology and therapeutic use in epilepsy. Drugs. 50 (4): 691-713. doi: 10.2165/00003495-199550040-00008
  3. Culy CR, Goa KL (2000) Lamotrigine: a review of its use in childhood epilepsy. Paediatric Drugs. 2 (4): 299-330. doi: 10.2165/00128072-200002040-00006
  4. Green AF, Sunil J (1999) Pharmaceutical composition containing lamotrigine. US5942510A. United States.
  5. Rees RWA, Russell PB, Foell TJ, Bright RE (1972) Antimalarial activities of some 3,5-diamino-as-triazine derivatives. Journal of Medical Chemistry. 15 (8): 859-861. doi: 10.1021/jm00278a024
  6. Rees WA, Russel PB (1972) 6-(Fluoro and trifluoromethyl phenyl)-3,5-diamino-1,2,4-triazines and substituted-6-phenylalkyl-3,5-diamino-1,2,4-triazines. US3637688A. United States.
  7. Rosenberg FJ, Bottiroli JA (1964) Antimalarials and other anticonvulsant drugs: Predictive validity of laboratory tests. Experimental Biology and Medicine. 115 (2): 410-414. doi. 0.3181/00379727-115-28927
  8. Baxter MG, Elphick AR, Miller AA, Sawyer DA (1981) 1,2,4-Triazine derivatives, process for preparing such compounds and pharmaceutical compositions containing them. EP0021121A1. European Patent Office.
  9. Allan G, Miller AA, Sawyer DA (1987) 1,2,4-triazines. US4649139A. United States.
  10. Sawyer DA, Copp FC (1991) Triazine salt. EP0247892B1. European Patent Office.
  11. Winter RG, Sawyer DA, Germain A (1996) Process for the preparation of lamotrigine. WO1996020934A1. WIPO (PCT).
  12. Lee GR (1999) Process for the preparation of lamotrigine. US5925755A. United States.
  13. Vyas SK (2000) An improved process for the preparation of 3,5-diamino-6-(2,3-dichlorophenyl)-l,2,4-triazine. WO2000035888A1. WIPO (PCT).
  14. Edmeades LM, Arthur N, Skinner G, Hill DA, Hill GT, Packham TW (2001) Compound and its use. US6333198B1. United States.
  15. Nadaka V, Lexmer J, Kaspi J (2001) Process for preparing substituted benzoyl cyanide amidinohydrazones. US6329521B2. United States.
  16. Guntoori BR, Che D, Murthy KSK (2003) Efficient process for the preparation of lamotrigine and related 3.5-diamino-6-substituted-1, 2,4-triazines. US6586593B1. United States.
  17. Radhakrishnan TV, Sasikumar TM, Srivastava AR (2003) Process for the preparation of 6-(2, 3-dichloro-phenyl)-1,2,4-triazine-3,5-diamine, commonly known as lamotrigine. US6639072B1. United States.
  18. Manjunatha SG, Kulkarni AK, Kishore C, Bokka R (2004) Crystalline lamotrigine and its monohydrate. GB2395483A. United Kingdom.
  19. Jozsef N, Tibor G, Jozsef T, Janos C, Ferenc V, Peter K, Gabor T (2004) New process for the synthesis of high purity 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine. WO2004026845A1. WIPO (PCT).
  20. Pere DB, Jordi BB (2004) Process for preparing a pharmaceutically active compound and for preparing its intermediate. WO2004039767A1. WIPO (PCT).
  21. Géza S, Csaba LG, Levente O, Attila GM, Ferenc L, Miklós N, Sándor G (2004) Method for producing Lamotrigine from alpha-oxo-2,3-dichlorophenyl acetamidino-aminoguandino hydrazone by ring closure reaction. US6683182B2. United States.
  22. Arul R, Dabholkar BV, Deore DB (2007) A novel process for the synthesis of lamotrigine and its intermediate. WO2007069265A1. WIPO (PCT).
  23. Dirk VD, Marc B, Frank B, Michel D, Alain L (2007) Method for preparing lamotrigine and its intermediate 2,3-dichlorobenzoyl chloride. WO2007138075A1. WIPO (PCT).
  24. Patel RB, Patel PR (2007) An improved process for preparation of lamotrigine intermediates. WO2007122638A2. WIPO (PCT).
  25. Paul RJ, Francis D (2008) A process for the preparation of lamotrigine. WO2008019798A1. WIPO (PCT).
  26. Jiang Y (2011) Method for preparing lamotrigine. CN102070545B. China.
  27. Yang Y, Chen L, Zhang Y (2012) Synthetic method of drug lamotrigine for curing bipolar disorder and epilepsy. CN102766104A. China.
  28. Carmen AA (2012) Method for synthesizing lamotrigine. US2012142919. United States.
  29. Yiyue Y, Chengcheng Y, Xiaoping Z, Liqin S (2014) Preparation method of lamotrigine. CN103570637A. China.
  30. Luo J, Li W (2014) Preparation method of lamotrigine and intermediate thereof. CN103833660A. China.
  31. Cheng J, Lina C, Wei L, Tong Z, Lei C (2016) Improved synthesis process for lamotrigine. CN106083753A. China.
  32. Zuo J, Chen L, Chen K, Teng Y, He M, Chen J (2018) Improved method for synthesizing lamotrigine. CN108129409A. China.
  33. Li S, Wang Y (2021) Crystal form of lamotrigine hydrate, preparation method thereof and composition containing same. CN113214177A. China.
  34. Saralaya SS, Kanakamajalu S (2023) A progressive review on the synthesis of atovaquone (an anti-malarial drug), empowered by the critical examination of prior-art disclosures, Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 3 (4): 33-53. doi: 10.5281/zenodo.10208022
  35. Saralaya SS, Shashiprabha, Kanakamajalu S (2023) A comprehensive review of the disclosed approaches for the synthesis of Parvaquone, an anti-protozoan drug. Journal of Chemical Sciences. 135 (2): 26. doi: 10.1007/ s12039-023-02145-6
  36. Saralaya SS, Shashiprabha, Kanakamajalu S (2023) A comprehensive review on the therapeutic applications and synthetic approaches of Buparvaquone. Mapana Journal of Sciences. 22 (2): 141-168. doi: 10.12723/ mjs.65.10
  37. Sanjay SS (2023) An exhaustive methodological review of patents on the synthesis and purification of Zoledronic acid. World Journal of Pharmaceutical Research. 12 (9): 2731-2777. doi: 10.20959/wjpr20239-28454
  38. Saralaya SS (2023) An overview of solvent-free and solvent/s-involved phosphorylation to synthesize zoledronic acid. Indian Journal of Pharmacy and Drug Studies. 2 (3): 107-112. doi: Nil.
  39. Saralaya SS (2023) An overview of prior patents for the sequential progress in the synthetic approaches of Rasagiline, its salts, crystallographic forms and impurities. Indian Journal of Pharmacy and Drug Studies.  2 (4): 132-147. doi: Nil.
  40. Kumar R, Kumar N, Roy R, Singh A (2017) Triazines-A comprehensive review of their synthesis and diverse biological importance, Current Medical and Drug Research. 1 (1): 1-12. Article ID 173. doi: Nil.

Submitted date:
02/02/2024

Reviewed date:
02/20/2024

Accepted date:
02/23/2024

Publication date:
02/23/2024

65d8f353a9539561e508b5c3 medjpps Articles
Links & Downloads

Mediterr J Pharm Pharm Sci

Share this page
Page Sections