1306760-87-1 Usage
Uses
Ozanimod is an agonist that binds to S1P1 and S1P5 receptors. Experiments on rodents revealed that Ozanimod is effective against autoimmune diseases.
Description
Ozanimod is a sphingosine-1-phosphate receptor 1 (S1P1) and S1P5 agonist. It induces GTPγS binding in cell membranes expressing human S1P1 or S1P5 (EC50s = 0.41 and 11 nM, respectively) but not cell membranes expressing S1P2 or S1P3 receptors (EC50s = >10,000 nM for both). Ozanimod (0.2 mg/kg) reduces the number of peripheral lymphocytes in rats. It reduces disease severity and the number of circulating lymphocytes in a mouse model of experimental autoimmune encephalomyelitis (EAE). Ozanimod (0.3 and 1 mg/kg) reduces disease severity and body weight loss in a mouse model of TNBS-induced colitis. Formulations containing ozanimod have been used in the treatment of relapsing multiple sclerosis and ulcerative colitis.
in vitro
ozanimod(rpc1063) was a specific agonist for s1p1 and s1p5 receptors. the ec50values were 160 ± 60 pm and 410 ± 160 pm for s1p1 receptors in the inhibition of camp generation and[35s]-gtpγs binding. the 83% emax value of ozanimod against s1p5 receptor was 11 ± 4.3 nm. rpc1063 dose-dependently decreased s1p1 receptor re-expression on the cell surface and resulted in near complete and sustained loss of cell surface receptor expression at concentrations above 10 nm in s1p1 receptor-hek293t cells after 1 h incubation [1].
in vivo
the t1/2 of ozanimod was 4.7 h and 5.1 h in mice and rats after p.o. administration, respectively. about 81–82% decrease in circulating t lymphocyte was observed after dosing administration for 6 h, with a maximal blood concentration of 45 nm and 159 nm in rats and mice respectively. oral gavage of ozanimod dose-dependently reduced the disease score of mice in both doses (0.2 or 0.6 mg/kg/day) [1].
Enzyme inhibitor
This orally available S1PR1 modulator (FW = 404.46 g/mol; CAS 1306760- 87-1; Solubility: 81 mg/mL DMSO; < 1 mg/mL H2O), also named RPC1063 and 5-[3-[(1S)-2,3-dihydro-1-[(2-hydroxyethyl)amino]-1H-inden- 4-yl]-1,2,4-oxadiazol-5-yl]-2-(1-methylethoxy)benzonitrile, selectively targets sphingosine 1-Phosphate (S1P) receptors, which mediate multiple processes, including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Ozanimod is specific for S1P1R (IC50 = 0.4 nM) and S1P5R, inducing S1P1R internalization and reversibly reducing the number of circulating B and CCR7+ T lymphocytes in vivo. It shows high oral bioavailability and volume of distribution, and a circulatory half-life that supports once daily dosing. Oral ozanimod reduced inflammation and disease parameters in three autoimmune disease models, commending its use in the treatment of relapsing multiple sclerosis (RMS) and inflammatory bowel disease (IBD). Indeed, the safety and efficacy of this modulator ozanimod in relapsing multiple sclerosis is indicated on the basis of a randomized, placebo-controlled, Phase 2 trial. Other SIPR1-directed immunomodulators include laquinimod, ponesimod, and siponimod.
references
scott f l, clemons b, brooks j, et al. ozanimod (rpc1063) is a potent sphingosine‐1‐phosphate receptor‐1 (s1p1) and receptor‐5 (s1p5) agonist with autoimmune disease‐modifying activity[j]. british journal of pharmacology, 2016.sandborn wj, feagan bg1, et al. ozanimod induction and maintenance treatment for ulcerative colitis. n engl j med. 2016, 374(18):1754-1762.
Check Digit Verification of cas no
The CAS Registry Mumber 1306760-87-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,0,6,7,6 and 0 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1306760-87:
(9*1)+(8*3)+(7*0)+(6*6)+(5*7)+(4*6)+(3*0)+(2*8)+(1*7)=151
151 % 10 = 1
So 1306760-87-1 is a valid CAS Registry Number.
1306760-87-1Relevant articles and documents
Enantioselective Synthesis of Ozanimod, the Active Pharmaceutical Ingredient of a New Drug for Multiple Sclerosis
Cianferotti, Claudio,Barreca, Giuseppe,Bollabathini, Venkatesh,Carcone, Luca,Grainger, Damian,Staniland, Samantha,Taddei, Maurizio
, p. 1924 - 1930 (2021/04/05)
We report here a short enantioselective synthesis of Ozanimod, a potent modulator of the enzyme Sphingosine-1-phosphate receptor (S1PR), recently approved by FDA and EMA for the treatment of relapsing-remitting multiple sclerosis. Amongst different synthetic approaches explored, we achieved the best result introducing the stereogenic centre in the last step through imine asymmetric transfer hydrogenation (ATH) using Wills’ catalysts. Besides the reduced numbers of enantiomeric purity controls required, this process culminates in an exceptionally high enantioselective reductive amination obtained with commercially available tethered Ru catalysts. Starting from commercially available 4-cyano-indanone, enantiomerically pure Ozanimod was obtained in 5 steps in 62 % overall yield and 99 % ee.
IMPROVED PROCESS FOR PREPARING OZANIMOD
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, (2020/07/04)
The presented invention relates to a process for preparation of compound of formula (1) or a salt thereof (i.e.) ozanimod : (1). The invention also relates to intermediates used in the process.
A PROCESS FOR THE PREPARATION OF OZANIMOD AND ITS INTERMEDIATE (S)-1-AMINO-2,3-DIHYDRO-1H-INDENE-4-CARBONITRILE
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Page/Page column 18-20, (2020/05/07)
The present invention relates to an improved process for preparation of Ozanimod (I) or pharmaceutically acceptable salts thereof. The present invention also relates to an improved process for preparation of (S)-l-amino-2,3-dihydro- 1H-indene-4-carbonitrile (II) or its optically active acid salts.