Cetilistat: Pharmacology and Clinical Studies

Cetilistat is a selective pancreatic lipase inhibitor approved in Japan in September 2013 for the treatment of obesity. The drug was discovered by Alizyme PLC and co-developed with Takeda. In a 12-week clinical trial, Cetilistat demonstrated a lower incidence of gastrointestinal adverse events and comparable weight loss compared to other approved weight loss therapies.

Figure 1. Cetilistat

Properties of Cetilistat

The molecular formula of Cetilistat is C7H5NO, the molecular weight is 119.12, it is white needle-shaped crystals or pale yellow crystals, the melting point is 110℃-113℃, and the boiling point is 145℃/266.6Pa. Cetilistat is slightly soluble in water and soluble in organic solvents such as methanol, acetone, ether, and chloroform.

Mechanism of Action

Cetilistat is a gastrointestinal lipase inhibitor that blocks the digestion and absorption of fat, thereby reducing energy intake and thus weight loss. It differs from most other weight loss drugs in that it does not act on the brain to reduce appetite, but rather on the periphery. The compound remains in the gastrointestinal tract and is not significantly absorbed by the body.

Synthesis of Cetilistat

The synthesis of Cetilistat is generally carried out as follows: first, commercially available hexadecanol is reacted with phosgene in tetrahydrofuran/toluene to produce the corresponding chloroformate, which is then immediately reacted with commercially available 2-amino-5-methylbenzoic acid in pyridine, and then methyl chloroformate is slowly added at room temperature to produce Cetilistat, with a total yield of 31%.

Safety of Cetilistat

In terms of safety, the risk terms of Cetilistat include R22 (harmful if swallowed), R36/37/38 (irritation to eyes, respiratory tract, and skin), and the safety terms are S24/25 (prevent skin and eye contact) and S45 (seek medical attention immediately and show the label in case of accident or discomfort).

Uses of Cetilistat

Cetilistat has a wide range of uses, including as an intermediate for pesticides, medicines, dyes, and liquid crystal materials. It is an intermediate for the herbicide bromoxynil and the insecticides fenthion and fenthion. In addition, Cetilistat is also an intermediate for liquid crystal materials, fragrances, etc.

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