Tamibarotene (brand name: Amnolake), also called retinobenzoic acid, is orally active, synthetic

retinoid The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout t ...

, developed to overcome

all-trans retinoic acid Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth f ...

(ATRA) resistance, with potential antineoplastic activity against acute promyelocytic leukaemia (APL) . It is currently marketed only in Japan and early trials have demonstrated that it tends to be better tolerated than ATRA. It has also been investigated as a possible treatment for

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

and

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

. 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.

Synthesis

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

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).Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, (1993).

References

Retinoids Antineoplastic drugs Benzoic acids Tetralins SRI International {{Antineoplastic-drug-stub