Tamibarotene

Tamibarotene

Tamibarotene
Identifiers
CAS number
PubChem
ChemSpider
DrugBank
ChEMBL
Beilstein Reference 3564473
Jmol-3D images Image 1
Properties
Molecular formula C22H25NO3
Molar mass 351.44 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)

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]

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).[4]

References

  1. ^ "Tamibarotene: AM 80, retinobenzoic acid, Tamibaro". Drugs in R&D 5 (6): 359–62. 2004.  
  2. ^ a b Miwako, I; Kagechika, H (August 2007). "Tamibarotene". Drugs Today (Barc) 43 (8): 563–568.  
  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.  
  4. ^ Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, U.S. Patent 5,214,202 (1993).