248281-84-7

Laquinimod (248281-84-7) is an immunomodulator1 that inhibits inflammation2 and autoimmunity3,4 via activation of the aryl hydrocarbon receptor (AhR)5. It has been investigated as a treatment for multiple sclerosis6 and has shown efficacy in Huntington’s disease models7,8.

Laquinimod (ABR-215062), an orally available carboxamide derivative, is a potent immunomodulator which prevents neurodegeneration and inflammation in the central nervous system. Laquinimod reduces astrocytic NF-κB activation to protect from Cuprizone-induced demyelination. Laquinimod has?the?potential?for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases?research[1][2][3][4].

ChEBI: Laquinimod is an aromatic amide.

b) To a stirred solution of anhydrous tetrahydrofuran (50 mL) of the compound (CAS:1379595-99-9) (10 mmol) was added sodium methanolate (3.6 mmol, 0.5 M, dissolved in methanol) in batches under nitrogen protection. The reaction mixture was heated to reflux for 2 hours. Upon completion of the reaction, the mixture was cooled and the solvent was partially evaporated to give a concentrated solution containing the insoluble salt. The concentrated solution was dissolved in a solvent mixture of methanol (30 mL), 10 M aqueous sodium hydroxide (1.07 mL, 10.7 mmol) and water (15.0 mL). Subsequently, 5 M aqueous hydrochloric acid (2.4 mL, 12.0 mmol) was slowly added to neutralize the reaction mixture. The precipitated crystalline precipitate was collected by filtration, washed with cold methanol and dried to afford the target product 5-chloro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide in 87% yield and 98.9% purity.

abr-215062 was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (eae) [1].

abr-215062 dose-dependently inhibited disease and showed better disease inhibitory effects as compared to roquinimex (linomide). furthermore, abr-215062 inhibited the inflammation of both cd4+ t cells and macrophages into central nervous tissues [2].

NF-κB

J?nsson et al. (2004), Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders: Structure-Activity Relationship; Med. Chem. 47 2075 Rothhammer et al. (2021); Aryl Hydrocarbon Receptor Activation in Astrocytes by Laquinimod Ameliorates Autoimmune Inflammation in the CNS, Neurol. Neuroimmunol. Neuroinflamm., 8 e946 Pitarokoili et al. (2014), Laquinimod exerts strong clinical and immunomodulatory effects in Lewis rat experimental autoimmune neuritis; Neuroimmunol., 274 38 Ott et al. (2019), Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity; Neuroinflammation, 16 49 Kaye et al. (2016), Laquinimod arrests experimental autoimmune encephalitis by activating the aryl hydrocarbon receptor; Natl. Acad. Sci. USA., 113 E6145 Th?ne and Linker (2016), Laquinimod in the treatment of multiple sclerosis: a review of the data so far; Drug Des. Devel. Ther., 10 1111 Dobson et al. (2016), Laquinimod dampens hyperactive cytokine production in Huntington’s disease patient myeloid cells; Neurochem., 137 782 Garcia-Miralles et al. (2016), Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of Huntington disease; Rep., 6 31652