Tamibarotene
Names
Preferred IUPAC name
4-[(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid
Identifiers
3D model (JSmol)
3564473
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
UNII
  • InChI=1S/C22H25NO3/c1-21(2)11-12-22(3,4)18-13-16(9-10-17(18)21)23-19(24)14-5-7-15(8-6-14)20(25)26/h5-10,13H,11-12H2,1-4H3,(H,23,24)(H,25,26)
  • O=C(O)c1ccc(cc1)C(=O)Nc2ccc3c(c2)C(CCC3(C)C)(C)C
Properties
C22H25NO3
Molar mass 351.446 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Tamibarotene (brand name: Amnolake), also called retinobenzoic acid, is orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity against acute promyelocytic leukaemia (APL) .[1] It is currently marketed only in Japan and early trials have demonstrated that it tends to be better tolerated than ATRA.[2] It has also been investigated as a possible treatment for Alzheimer's disease, multiple myeloma and Crohn's disease.[2][3] Tamibarotene is found to have inhibitory potential for the viral spike protein of Omicron variant of SARS-CoV2 and can be a potential candidate for developing potential therapeutics for the treatment of omicron variant of COVID19.[4]

Synthesis

The tetralin-based compound tamibarotene (7) has been tested as an agent for treating leukaemias.

Reaction of the diol (1) with hydrogen chloride affords the corresponding dichloro derivative (2). Aluminum chloride mediated Friedel–Crafts alkylation of acetanilide with the dichloride affords the tetralin (3). Basic hydrolysis leads to the primary amine (4). Acylation of the primary amino group with the half acid chloride half ester from terephthalic acid (5) leads to the amide (6). Basic hydrolysis of the ester grouping then affords (7).[5]

References

  1. ↑ "Tamibarotene: AM 80, retinobenzoic acid, Tamibaro". Drugs in R&D. 5 (6): 359–62. 2004. doi:10.2165/00126839-200405060-00010. PMID 15563242.
  2. 1 2 Miwako, I; Kagechika, H (August 2007). "Tamibarotene". Drugs of Today. 43 (8): 563–568. doi:10.1358/dot.2007.43.8.1072615. PMID 17925887.
  3. ↑ Fukasawa, H; Nakagomi, M; Yamagata, N; Katsuki, H; Kawahara, K; Kitaoka, K; Miki, T; Shudo, K (2012). "Tamibarotene: a candidate retinoid drug for Alzheimer's disease" (PDF). Biological & Pharmaceutical Bulletin. 35 (8): 1206–1212. doi:10.1248/bpb.b12-00314. PMID 22863914.
  4. ↑ Mujwar S. Computational repurposing of tamibarotene against triple mutant variant of SARS-CoV-2. Comput Biol Med. 2021 Sep;136:104748. doi: 10.1016/j.compbiomed.2021.104748. Epub 2021 Aug 8. PMID: 34388463; PMCID: PMC8349365.
  5. ↑ Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, U.S. Patent 5,214,202 (1993).


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