Tamibarotene Explained

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] Tamibarotene has been tested in many other cancer types, including Acute Myeloid Leukemia where it shows no benefit[3], and lung cancer, where it accelerated the cancer growth and increased mortality[4] .

It has also been investigated as a possible treatment for Alzheimer's disease, multiple myeloma and Crohn's disease.[5] Tamibarotene shows a similar side effect profile to Tretinoin, but exhibits lower clearance, resulting in improved dosing regiments. Hyperlipidemia is a common finding from Tamibarotene dosing[6] .

Synthesis

Reaction of thediol (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 tothe amide (6). Basic hydrolysis of the ester grouping then affords (7).[7]

Notes and References

  1. 15563242 . 2004 . Tamibarotene: AM 80, retinobenzoic acid, Tamibaro . 5 . 6 . 359–62 . Drugs in R&D . 10.2165/00126839-200405060-00010. 34546131 .
  2. Tamibarotene. Drugs of Today. August 2007. 43. 8. 563–568. 10.1358/dot.2007.43.8.1072615. 17925887. Miwako, I . Kagechika, H .
  3. Web site: 2024-08-12 . Syros Provides Update on SELECT-AML-1 Phase 2 Clinical Trial :: Syros Pharmaceuticals, Inc. (SYRS) . 2024-08-15 . Syros Pharmaceuticals, Inc. . en.
  4. Arrieta . Oscar . Levitt . Daniel J. . Pendergrass . Kelly B. . Gladkov . Oleg . Bondarenko . Igor . Jain . Minish Mahendra . Wieland . Scott . 2015-05-20 . Efficacy and safety of adding the retinoid tamibarotene or placebo to paclitaxel/carboplatin for advanced non-small cell lung cancer. . Journal of Clinical Oncology . en . 33 . 15_suppl . e19034–e19034 . 10.1200/jco.2015.33.15_suppl.e19034 . 0732-183X.
  5. Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biological & Pharmaceutical Bulletin. 2012. 35. 8. 1206–1212. 10.1248/bpb.b12-00314. 22863914. Fukasawa, H . Nakagomi, M . Yamagata, N . Katsuki, H . Kawahara, K . Kitaoka, K . Miki, T . Shudo, K . PDF. free.
  6. Arrieta . Oscar . Levitt . Daniel J. . Pendergrass . Kelly B. . Gladkov . Oleg . Bondarenko . Igor . Jain . Minish Mahendra . Wieland . Scott . 2015-05-20 . Efficacy and safety of adding the retinoid tamibarotene or placebo to paclitaxel/carboplatin for advanced non-small cell lung cancer. . Journal of Clinical Oncology . en . 33 . 15_suppl . e19034–e19034 . 10.1200/jco.2015.33.15_suppl.e19034 . 0732-183X.
  7. Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, (1993).

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