FESOTERODINE Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses

Fesoterodine

IUPAC nomenclature

[2-[(1R)-3-(Di(propan-2-yl)amino)-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate

 

Classification

Fesoterodine is an acetylcholine antagonist. It is a muscarinic antagonist.

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 411.6 g/mol
2 Physical appearance Solid
3 Melting point 104-107°C
4 Solubility Highly soluble
5 Presence of ring Benzene
6 Number of chiral centers 1
 

 

Mechanism of Action

Fesoterodine converts into its active metabolite, 5-hydroxymethyltolterodine. The active metabolite acts as a muscarinic antagonist, which helps in inhibition of bladder contraction and decreases the detrusor pressure. [1]

 

Structure Activity Relationship

  • Either R1 or R2 must be heterocyclic or carbocyclic.
  • The R3 group can be hydrogen, hydroxyl, hydroxymethyl or amide.
  • Most potent derivatives has X as an ester.
  • X can also be either oxygen or absent completely.
  • The N substituent can be quaternary ammonium salt or tertiary amine or both with different alkyl groups.
  • Maximum potency obtained when the distance between the ring substituted carbons is 2 carbon units.

 

Method of synthesis

i. Reaction of methyl-4-hydroxy benzoate with 3-diisopropylamino-1-phenyl propanol in presence of methane sulfonic acid to give 3-(3-diisopropyl amino-1-phenylpropyl)-4-hydroxy benzoate.

ii. Resolution of the above formed product with(+)2,3-dibezoyl-D-tartaric acid in ethanol produces (+)2,3-dibenzoyl –D-tartaric acid of 3-(3-diisopropyl amino-1-phenyl-propyl)-4-hydroxy benzoate.

iii. The product is then reduces with Lithium aluminum hydride to give R-(+)-2-(3-diisopropylamino-1-phenyl-propyl)-4-hydroxy methyl-phenol.

iv. On reaction of the latter compound with isobutyl chloride produces Fesoterodine. [2]

Therapeutic Uses

Fesoterodine is used for:

  • Treatment of overactive bladder
  • Reducing the frequent trips to bathroom
  • Reducing the urge for frequent voids
  • Reducing the leakage of urine

 

Side Effects

Side effects of Fesoterodine are:

  • Constipation
  • Headache
  • Dry mouth
  • Blurred vision
  • Dry eyes

MCQ

Q.1 Match the following with correct SAR of the drug fesoterodine-

i. When X is an ester A. Maximum potency
ii. Distance between the ring substituted carbons is 2 carbon unit B.Minimum potency
. C. Least potent derivative
  D. Most potent derivative

 a) i-A, ii-D

b) i-A, ii-C

c) i-B, ii-C

d) i-C, ii-D

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

  • Benztropin: (3-endo)-3-(Diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane
  • Fesoterodine: [2-[(1R)-3-(Di(propan-2-yl)amino)-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate
  • Flurazepam: 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
  • Midazolam: 7-Chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

a) TFTF

b) TTFF

c) FFTT

d) TTFT

Q.3 Number of chiral carbons present in the structure of Fesoterodine?

a) 0

b) 1

c) 2

d) 3

Q.4 The active metabolite of fesoterodine, 5-hydroxymethyltolterodine acts as??

a) Mixed agonist

b) Nicotinic antagonist

c) Muscarinic antagonist

d) ß-inhibitor

Q.5 Which amongst the following is a therapeutic use of drug fesoterodine?

a) Treatment of Insomia

b) Treatment of Alzhiemer’s disease

c) Treatment of Overactive bladder

d) Treatment of Asthma

Q.6 Which of the following drug and their classification are correct?

I. Benztropin: acetylcholine antagonist

II. Fesoterodine: Nitrogen mustard

III. Flurazepam: benzodiazepine sedative hypnotic

IV. Midazolam: Acetylcholine Nicotinic receptor antagonist

a) I, III

b) I, III, IV

c) II, IV

d) I, II, III, IV 

Q.7 Type of ring present in the structure of fesoterodine is?

a) Benzene

b) Pyrimidine

c) Pyrolopyrimidine

d) Not present 

 

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ANSWERS

1-a

2-b

3-b

4-c

5-c

6-a

7-a

 

 

REFERENCES

[1] Vella M, Cardozo L. Review of fesoterodine. Expert opinion on drug safety. 2011 Sep 1;10(5):805-8.

[2] Arava V, Bandatmakuru S. Synthesis of fesoterodine: An enantiopure active pharmaceutical ingredient (API). Journal of Chemical and Pharmaceutical Research. 2016;8(8):518-38.

 

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