Ponesimod

Ponesimod is a next-generation S1P receptor modulator approved for the treatment of relapsing multiple sclerosis, offering an alternative to first-in-class agents in this therapeutic category. As an immunomodulator, Ponesimod prevents lymphocyte egress from lymph nodes by functionally antagonizing S1P₁ signaling, thereby reducing the number of circulating peripheral lymphocytes and limiting lymphocyte infiltration into target tissues. In preclinical studies, Ponesimod demonstrated protection against lymphocyte-mediated tissue inflammation, prevented edema formation and inflammatory cell accumulation in delayed-type hypersensitivity models, and reduced paw volume and joint inflammation in adjuvant-induced arthritis models. Additionally, Ponesimod has been investigated for the treatment of psoriasis, highlighting its broad potential in autoimmune and inflammatory conditions.

 

Product Parameters

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Parameter	Specification
Product Name	Ponesimod
CAS Number	854107-55-4
Molecular Formula	C₂₃H₂₅ClN₂O₄S
Molecular Weight	460.97 g/mol
Appearance	Light yellow to yellow solid
Boiling Point	658.0 ± 65.0 °C at 760 Torr
Density	1.30 ± 0.1 g/cm³ at 20 °C
Storage Condition	-20°C

 

Mechanism Of Action

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Ponesimod is a selective sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) agonist. S1P is an intracellular signaling molecule involved in various biological processes, including cell migration and survival. By binding to the S1P1 receptor, ponesimod induces receptor internalization, thereby inhibiting lymphocyte efflux from lymph nodes. This effect reduces the number of lymphocytes in the bloodstream and limits their migration to inflammatory sites, contributing to the slowing of disease progression in multiple sclerosis.

 

Application

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Ponesimod is an oral medication developed by Janssen Pharmaceuticals, a division of Johnson & Johnson, which was approved in 2021 for the treatment of relapsing multiple sclerosis (MS).

 

Synthetic Route

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The synthesis of Ponesimod involves a three-component coupling reaction using isothiocyanate 16.1, n-propylamine, and 2-bromoacetyl bromide 16.2 to construct the thiazolidine-4-one core 16.3. The regioselectivity of this cyclization is highly dependent on the selected halogenated acetic acid derivative; in this case, 2-bromoacetyl bromide 16.2 demonstrated high regioselectivity for the desired product 16.3 (ratio 41:1, 16.3:16.4), whereas 2-bromoacetamide exhibited lower selectivity (ratio 1:10,16.3:16.4). Subsequently, an aldol condensation reaction with aldehyde 16.5 was carried out to yield phenol 16.6, achieving overall high yields starting from the initial isothiocyanate 16.1. The final step involved the SN2-mediated coupling of chiral chloropropanediol 16.7 to phenol 16.6 in the presence of a base, resulting in the final synthesis of Ponesimod.

 

Contact Us

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Need Ponesimod for your multiple sclerosis research, immunology studies, or drug development program? Cosperpharm is ready to supply high-purity material with the documentation and support you require. Reach out today — our team is here to help you move your project forward.