1230487-00-9

Basic information

• Product Name: BAF-312(SiponiMod)
• Synonyms: BAF-312(SiponiMod);SiponiMod;(E)-1-(4-(1-(4-cyclohexyl-3-(trifluoromethyl)benzyloxyimino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid;BAF312 (Siponimod) 1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid;3-Azetidinecarboxylic acid, 1-[[4-[(1E)-1-[[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-;1-(4-[1-[(E)-4-Cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl]-2-ethyl-benzyl)-azetidine-3-carboxylic acid
• CAS NO: 1230487-00-9
• Molecular Formula: C₂₉H₃₅F₃N₂O₃
• Molecular Weight: 516.5950096
• Product Categories: API;Inhibitors
• Mol File: 1230487-00-9.mol

Chemical Properties

• Boiling Point: 602.0±65.0 °C(Predicted)
• Appearance: /
• Density: 1.24±0.1 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.69±0.20(Predicted)
• CAS DataBase Reference: BAF-312(SiponiMod)(CAS DataBase Reference)
• NIST Chemistry Reference: BAF-312(SiponiMod)(1230487-00-9)
• EPA Substance Registry System: BAF-312(SiponiMod)(1230487-00-9)

Safety Data

• Hazardous Substances Data: 1230487-00-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
BAF-312 (SiponiMod) is used as a treatment for multiple sclerosis and other central nervous system-related diseases in human subjects. It modulates the immune system by selectively targeting S1P receptor subtypes 1 and 5, which may lead to an improved adverse event profile compared to other S1P receptor modulators.
Used in Research and Development:
BAF-312 (SiponiMod) is used as a research tool for studying the role of S1P signaling in immune, cardiovascular, and central nervous system functions. Its selectivity for specific S1P receptor subtypes allows researchers to investigate the underlying mechanisms and potential therapeutic applications in various diseases and conditions.

Side effects

Siponimod,2 mg/day, was studied in a Phase I placebo-controlled trial in patients with secondary progressive Ms.206The primary endpoint was time to 3 months confirmed dis- ability progression. There were substantive side effects from the drug，mainly increased liver transaminase concentrations,bradycardia, and bradyarrhythmia at treatment initiation.With subsequent siponimod administration，there was an increased incidence of macular edema, hypertension,varicella zoster reactivation, and convulsions compared to placebo. By grad- ually escalating the initial dose of siponimod, cardiac first-dose effects were reduced.While the results of this trial are encouraging,long- term safety issues may be a greater concern5or since persons with secondary progressive MS as a group are older,with a higher incidence of comorbidities that could preclude use of siponimod.

references

[1] gergely p1, nuesslein-hildesheim b, guerini d, brinkmann v, traebert m, bruns c, pan s, gray ns, hinterding k, cooke ng, groenewegen a, vitaliti a, sing t, luttringer o, yang j, gardin a, wang n, crumb wj jr, saltzman m, rosenberg m, wallstr?m e. the selective sphingosine 1-phosphate receptor modulator baf312 redirects lymphocyte distribution and has species-specific effects on heart rate. br j pharmacol. 2012 nov;167(5):1035-47. [2] pan s1, gray ns1, gao w1, mi y1, fan y1, wang x1, tuntland t1, che j1, lefebvre s1, chen y1, chu a1, hinterding k2, gardin a2, end p2, heining p2, bruns c2, cooke ng2, nuesslein-hildesheim b2 .discovery of baf312 (siponimod), a potent and selective s1p receptor modulator. acs med chem lett. 2013 jan 4;4(3):333-7.

Upstream product

• 800379-62-8 O-(4-cyclohexyl-3-trifluoromethyl-benzyl)-hydroxylamine 
• 957205-24-2 4-(chloromethyl)-1-cyclohexyl-2-(trifluoromethyl)benzene 
• 909190-70-1 1-[3-bromo-4-(bromomethyl)phenyl]ethan-1-one 
• 1378888-43-7 1-[3-ethyl-4-(hydroxymethyl)phenyl]ethan-1-one 
• 108-94-1 cyclohexanone 
• 392-83-6 o-trifluoromethylphenyl bromide 
• 13376-26-6 1-cyclohex-1-enyl-2-trifluoromethylbenzene 
• 1449293-48-4 1-cyclohexyl-4-methyl-2-trifluoromethylbenzene 

Relevant articles and documents

METHODS FOR THE PREPARATION OF SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATORS AND SOLID FORMS THEREOF

The present invention relates to process for preparation of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxy imino]ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid, intermediates, salts and solid forms thereof to pharmaceutical compositions comprising the salts and solid forms and to use of said compositions for the treatment of multiple sclerosis, particularly secondary progressive multiple sclerosis.

PROCESS FOR MAKING SIPONIMOD AND INTERMEDIATE THEREOF

The presented invention relates to a process for preparation of compound of formula (I) or a salt or a solvate thereof (i.e.) siponimod. The invention also relates to intermediates used in the process and solid forms of these intermediates.

SOLID STATE FORMS OF SIPONIMOD

The present application provides novel polymorphic forms of siponimod, their processes, their use in purification of other crystalline polymorphic forms of siponimod, and pharmaceutical compositions containing them. The present application specifically provides crystalline Form S, Form S1 and Form S2 of siponimod, their preparative methods, their use in purification of other crystalline forms of siponimod and pharmaceutical compositions thereof.

SOLID FORMS OF SIPONIMOD

The present invention relates to solid Form 1, Form 2, Form 3 and Form 6 of the compound Siponimod and processes for preparation thereof. The present invention further relates to processes for preparation of solid Form A of the compound Siponimod.

PROCESS FOR PREPARATION OF SIPONIMOD, ITS SALTS AND SOLID STATE FORMS THEREOF

The present application provides process for preparation of siponimod, intermediates of siponimod, salts of siponimod, polymorphic forms and solid dispersions of siponimod and its salts thereof. The present application specifically provides crystalline polymorphic forms of siponimod base, siponimod hemifumarate and other salts and pharmaceutical compositions thereof. Also provided are solid dispersions of siponimod hemifumarate and pharmaceutical compositions containing them.

AZETIDINE MODULATORS OF THE SPHINGOSINE 1-PHOSPHATE RECEPTOR

Described are deuterium-substituted azetidine compounds of Formula (I), which are modulators of sphingosine 1 -phosphate receptor. Also described are pharmaceutical compositions comprising the deuterium-substituted azetidine compounds, and methods of use thereof.

PROCESS FOR PREPARING N-(4-CYCLOHEXYL-3-TRIFLUOROMETHYL-BENZYLOXY)-ACETIMIDIC ACID ETHYL ESTER

This invention relates to novel processes for synthesizing N-(4-cyclohexyl-3-trifluoromethyl-benzyloxy)-acetimidic acid ethyl ester and to the compound of formula I and other intermediates that are used in such processes.

Discovery of BAF312 (Siponimod), a potent and selective S1P receptor modulator

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl) -2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing-remitting multiple sclerosis.

NEW POLYMORPHIC FORM OF 1- (4- { L- [ (E) -4-CYCLOHEXYL--3-TRIFLUOROMETHYL-BENZYLOXYIMINO] -ETHYL) -2-ETHYL-BENZY L) -AZETIDINE-3-CARBOXYLIC

This invention relates to a novel crystalline form (Form A) of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid (Compound I), to pharmaceutical compositions comprising this crystalline form, to processes for forming it and to its use in medical treatment.