286930-02-7 Usage
Description
Fesoterodine, launched for the treatment of OAB, is an orally
active pro-drug that is converted in vivo to its active metabolite 5-HMT
through hydrolysis by non-specific esterases. 5-HMT is also an active
metabolite of tolterodine (Detrol), which has been marketed for the
treatment of OAB since 1998. 5-HMT is a potent muscarinic antagonist,
with essentially equivalent affinity for M1, M2, M3, M4, and M5
receptors (Ki＝0.32, 0.63, 1.26, 2, and 0.63 nM, respectively). The binding
of 5-HMT is stereoselective; the corresponding S-enantiomer has at least
100 times lower binding affinity for all five receptors. Fesoterodine is
supplied as its fumarate salt in an extended release tablet form. The
recommended starting dose is 4 mg once daily. On the basis of individual
response and tolerability, the dose may be increased to 8 mg once
daily. Following oral administration, fesoterodine is not detected in the
peripheral blood, thereby indicating a rapid and complete bioconversion
to 5-HMT. Bioavailability of 5-HMT is about 52%. After single- or
multiple-dose oral administration of fesoterodine in doses from 4 to
28 mg, plasma concentrations of 5-HMT are proportional to the dose.
Maximum plasma levels are reached after approximately 5 h. No
accumulation occurs after multiple-dose administration. 5-HMT is further metabolized in the liver through oxidation of the hydroxymethyl
group and oxidative cleavage of N-alkyl groups mediated by CYP2D6
and CYP3A4. 5-HMT and its metabolites are primarily eliminated through renal excretion.The most common adverse events associated with fesoterodine include dry mouth, constipation, and dyspepsia. Fesoterodine is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma.
Originator
Schwarz Pharma (Germany)
Brand name
Toviaz
Synthesis
The chemical synthesis of fesoterodine starts with the cyclization of 4-(hydroxymethyl)phenol with cinnamaldehyde by means of piperazine in refluxing toluene to produce 2-hydroxy-6-(hydroxymethyl)-4-phenyl-3,4-dihydro-2H-1- benzopyran, which is subjected to reductive amination with To Market, To Market 2008 605 diisopropylamine by means of hydrogen over palladium hydroxide catalyst. The resultant racemic amine intermediate is optically resolved with (R)-(2)-acetoxy-2-phenylacetic acid to yield the corresponding (R)- enantiomer, which is finally acylated with isobutyryl chloride to afford fesoterodine.
Check Digit Verification of cas no
The CAS Registry Mumber 286930-02-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,8,6,9,3 and 0 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 286930-02:
(8*2)+(7*8)+(6*6)+(5*9)+(4*3)+(3*0)+(2*0)+(1*2)=167
167 % 10 = 7
So 286930-02-7 is a valid CAS Registry Number.
286930-02-7Relevant articles and documents
PROCESS FOR THE PREPARATION OF OPTICALLY PURE FESOTERODINE DERIVATIVES
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Paragraph 0245; 0246, (2015/04/15)
3,3-diphenylpropylamines of general formula (I), particularly Fesoterodine, as well as their enantiomers, solvates and salts, can be produced by treating a compound of formula (II) with a chiral alcohol to yield the diastereomeric esters of formula (IV) and (IV′), which can be further transformed into a compound of formula (I), or an enantiomer, solvate or salt thereof, wherein R1 is C1-C8 alkyl; and R2 and R3, independently of one another, represent H or C1-C6 alkyl, or together form a ring of 3 to 7 members with the nitrogen to which they are bound.
PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE 3,3-DIPHENYLPROPYLAMINES
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Page/Page column 35; 36, (2013/08/15)
The invention relates to a process for obtaining 3,3-diphenylpropylamines of general formula (I), particularly Fesoterodine, as well as their enantiomers, solvates and salts, comprising treating a compound of formula (II) with a chiral alcohol to yield the diastereomeric esters of formula (IV) and (IV'), which can be further transformed into a compound of formula (I), or an enantiomer, solvate or salt thereof, wherein R1 is C1-C8 alkyl; and R2 and R3, independently of one another, represent H or C1-C6 alkyl, or together form a ring of 3 to 7 members with the nitrogen to which they are bound.
"Process for the preparation of fesoterodine or a salt thereof"
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Page/Page column 7-8, (2012/06/18)
A process for the preparation of (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)-phenol isobutyrate (Fesoterodine) or a pharmaceutically acceptable salt thereof having low content in impurities.
