Bempedoic acid Chemical Properties

Melting point:

87 - 92°C

Boiling point:

506.5±35.0 °C(Predicted)

Density 

1.045±0.06 g/cm3(Predicted)

storage temp. 

Refrigerator

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

4.55±0.45(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C19H36O5/c1-18(2,16(21)22)13-9-5-7-11-15(20)12-8-6-10-14-19(3,4)17(23)24/h15,20H,5-14H2,1-4H3,(H,21,22)(H,23,24)

InChIKey

HYHMLYSLQUKXKP-UHFFFAOYSA-N

SMILES

C(O)(=O)C(C)(C)CCCCCC(O)CCCCCC(C)(C)C(O)=O

Bempedoic acid Usage And Synthesis

Description

Etc-1002 is a small molecule that can be used orally to lower LDL-C and is an activator of LIVER AMPK. ETC-1002 has an effective inhibitory effect on liver ATP-Citrate lyase.

Uses

ETC-1002 (Bempedoic acid, ESP-55016),also known as Bempedoic acid, is an orally available, once-daily LDL-C lowering small molecule designed to lower elevated levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies.ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK). It has potent inhibitory activity against hepatic ATP-citrate lyase(IC50=29 uM).

Definition

ChEBI: Bempedoic acid is an alpha,omega-dicarboxylic acid that is pentadecanedioic acid which is substituted by methyl groups groups at positions 2 and 14, and by a hydroxy group at position 8. It is a drug used for the treatment of high LDL cholesterol, which is sometimes referred to as 'bad cholesterol'. It has a role as an antilipemic drug, an EC 2.3.3.8 (ATP citrate synthase) inhibitor and a prodrug.

Indications

Bempedoic acid (ETC-1002) is a lipid-lowering agent approved by the FDA for use as an adjunct to maximally tolerated statin therapy for the reduction of LDL cholesterol, particularly in patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolaemia (HeFH).

brand name

NEXLETOL, NEXLIZET

Mechanism of action

Bempedoic acid (ETC-1002) inhibits cholesterol biosynthesis by inhibiting adenosine triphosphate-citrate lyase (ACL), which in turn inhibits cholesterol biosynthesis, leading to an increase in the expression of the LDL receptor and an enhancement of the plasma clearance of low-density lipoproteins (LDL-C). ETC-1002 is an orally active prodrug that is intracellularly activated. ETC-1002 activates AMPK, which in turn inhibits the production of pro-inflammatory cytokines and chemokines, and also contributes to the amelioration of diseases such as ASCVD and HeFH.

Synthesis

Starting from 317 kg of ethyl isobutyrate (147), alkylation with alkyl bromide (148) followed by Finkelstein reaction gave alkyl iodide 149. Alkyl iodide 149 was reacted with 0.5 equivalents of methanesulfonyl isocyanate under alkaline conditions to promote dialkylation of iodide 149 to give intermediate isonitrile 150. Intermediate isonitrile 150 was not isolated but directly treated in isopropionic acid under acidic conditions. Ketone 151 was generated in excellent yield based on the mass of isonitrile 150 by pH adjustment. Reduction of ketone 151 using sodium borohydride followed by saponification gave the crude active pharmaceutical ingredient (API). Bepedic acid was further isolated in high yield after a series of crystallization steps. Scale-up: Notably, this synthetic route has been demonstrated at a scale of over 300 kg.

Bempedoic acid(738606-46-7)Related Product Information

• Bempedoic Acid Impurity 1-d4
• Bempedoic Acid-d4