| Identification | Back Directory | [Name]
(2Z,5Z)-5-(3-chloro-4-((R)-2,3-dihydroxypropoxy)benzylidene)-2-(propyliMino)-3-(o-tolyl)thiazolidin-4-one | [CAS]
854107-55-4 | [Synonyms]
CS-2110
CS-2358
PonesiMod
ACT 128800
PONESIMOD,ACT-128800
ACT128800;ACT 128800;ACT-128800
(2Z,5Z)-5-(3-chloro-4-((R)-2,3-dihydroxypropoxy)benzylidene)-2-(propyliMino)-3-(o-tolyl)thiazolidin-4-one
5-[3-Chloro-4-[((2R)-2,3-dihydroxypropyl)oxy]benz-(Z)-ylidene]-2-((Z)-propylimino)-3-(o-tolyl)thiazolidin-4-one
(5Z)-5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]methylidene]-3-(2-methylphenyl)-2-propylimino-1,3-thiazolidin-4-one
4-Thiazolidinone, 5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]Methylene]-3-(2-Methylphenyl)-2-(propyliMino)-, (2Z,5Z)- | [Molecular Formula]
C23H25ClN2O4S | [MDL Number]
MFCD18207776 | [MOL File]
854107-55-4.mol | [Molecular Weight]
460.97 |
| Chemical Properties | Back Directory | [Boiling point ]
658.0±65.0 °C(Predicted) | [density ]
1.30±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
A crystalline solid | [pka]
13.38±0.20(Predicted) | [color ]
Off-white to yellow | [InChIKey]
LPAUOXUZGSBGDU-STDDISTJSA-N | [SMILES]
S1/C(=C\C2=CC=C(OC[C@H](O)CO)C(Cl)=C2)/C(=O)N(C2=CC=CC=C2C)/C/1=N/CCC |
| Safety Data | Back Directory | [WGK Germany ]
WGK 3 | [Storage Class]
6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | [Hazard Classifications]
Acute Tox. 4 Oral
Repr. 1B |
| Hazard Information | Back Directory | [Description]
Ponesimod is an oral drug developed by Johnson & Johnson's Janssen Pharmaceuticals unit and approved in 2021 for the treatment of relapsing multiple sclerosis (MS). MS is a chronic inflammatory disease that affects the central nervous system, resulting in neurological dysfunction and disability. | [Uses]
Ponesimod is an orally active sphingosine-1-phosphate receptor agonist. It protects against lymphocyte-mediated tissue inflammation. | [Brand name]
Ponvory | [Biological Activity]
ec50: 5.7 nmponesimod is a sphingosine-1-phosphate receptor 1 (s1p1) modulator.lymphocyte exit from lymph nodes and its recirculation into blood is reported to be controlled by s1p. the cellular receptor mediating lymphocyte exit is one of five s1p receptors, s1p1. thus, the nonselective agonists for s1p1 lead to blood lymphocyte count reduction. | [Mechanism of action]
Ponesimod is a selective sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) agonist. S1P is an intracellular signalling molecule involved in a variety of biological processes including cell migration and survival.Ponesimod works by binding to the S1P1 receptor, leading to internalisation of the receptor. thereby inhibiting the efflux of lymphocytes from the lymph nodes. This action reduces the number of lymphocytes in the blood and limits their ability to reach sites of inflammation, helping to slow the progression of multiple sclerosis. | [Synthesis]
Ponesimod was synthesised using a three-component coupling of isothiocyanate 16.1, n-propylamine and 2-bromoacetylbromide 16.2 to construct the thiazolidin-4-one parent nucleus 16.3.The regioselectivity of this cyclisation was heavily dependent on the haloacetic acid derivative chosen; in this case, 2-bromoacetylbromide 16.2 showed a high regioselectivity for the desired 16.3 (ratio 41:1, 16.3: 16.4) showed high regioselectivity, in contrast to the lower selectivity of methyl 2-bromoacetate (ratio 1:10, 16.3:16.4). Subsequent hydroxyaldol condensation (aldol-type condensation) with aldehyde 16.5 yielded phenol 16.6, and overall high yields were obtained from the starting isothiocyanate 16.1. The final step involved the attachment of chiral chloropropanediol 16.7 to phenol 16.6 via the SN2 mechanism in the presence of a base, resulting in the synthesis of Ponesimod (16).
 | [in vitro]
previous study found that ponesimod could activate s1p1-mediated signal transduction with high potency. moreover, relative to the potency for s1p, the potency of ponesimod at human recombinant receptors was 4.4-fold higher for s1p1 and 150-fold lower for human s1p3. thus, ponesimod was 650-fold more selective for human s1p1 over s1p3 than the endogeneous ligand [1]. | [in vivo]
animal study showed that the oral administration of ponesimod to rats resulted in a dose-dependent decrease of blood lymphocyte count, and the blood lymphocyte count returned to baseline within 48 h after discontinuation of ponesimod treatment. in addition, ponesimod prevented inflammatory cell accumulation, edema formation, as well as cytokine release in the skin of mice with delayed-type hypersensitivity. furthermore, in rats with adjuvant-induced arthritis, ponesimod could also prevent the increase in paw volume and joint inflammation [2]. | [IC 50]
S1PR1: 6 nM (IC50); S1PR5: 142 nM (IC50); S1PR4: 1956 nM (IC50); S1PR3: 2068 nM (IC50) | [storage]
Store at -20°C | [References]
[1] piali l, froidevaux s, hess p, nayler o, bolli mh, schlosser e, kohl c, steiner b, clozel m. the selective sphingosine 1-phosphate receptor 1 agonist ponesimod protects against lymphocyte-mediated tissue inflammation. j pharmacol exp ther. 2011 may;337(2):547-56.
[2] d'ambrosio d, freedman ms, prinz j. ponesimod, a selective s1p1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases. ther adv chronic dis. 2016 jan;7(1):18-33. |
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