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

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

Terbutaline

IUPAC nomenclature

(RS)-5-[2-(tert-Butylamino)-1-hydroxyethyl]benzene-1,3-diol.

 

Classification

Terbutaline is ß2-adrenergic agonist. [1]

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 225.28 g/mol
2 Physical appearance Present in solid form
3 Melting point 119-122°C
4 Solubility 213 mg/ml
5 Octanol/water partition coefficient 0.9
6 Presence of ring Benzene ring present
7 Number of chiral centers 1

 

Mechanism of Action

i. Adenyl cyclase enzyme is stimulated through the ß-adrenergic receptors.

ii. The conversion of ATP to cyclic AMP also increases due to this.

iii. Due to raise in level of CAMP, relaxation of bronchial smooth muscles and inhibition of release mediators of immediate hypersensitivity from mast cells takes place.

Structure Activity Relationship

  • Primary or secondary aliphatic amine separated by two carbons from a substituted benzene ring is essential for the high agonist activity.
  • The hydroxyl substituted carbon must be in the R configuration for the maximal direct activity.

R1 substitution:

  • When R1 is increased in size, activity of alpha receptors decreases and activity of the beta receptors increases
  • Activity of both alpha and beta receptors is maximum when R1 is methyl group.
  • Alpha agonist activity decreases when R1 is larger than methyl, and went negligible when R1 is isopropyl.
  • Large lipophillic groups can afford compounds with alpha blocking activity.
  • N-substituent provides selectivity for different receptors.
  • Arylalkyl group can provide beta selectivity, increased cell penetration and increased lipophillicity for the longer duration of action.

R2 substitution:

  • Ethyl group can eliminate the alpha activity of the drug.
  • Erythrostero isomers have maximal activity.
  • The additional methyl group makes the drug more selective for the alpha2

R3 substitution on the aromatic ring:

  • 3’,4’-dihydroxy substituted benzene ring has poor oral activity.
  • 3’, 5’-dihydroxy compounds are orally active.
  • At least one of the groups is required which can form hydrogen bonds. And if only one group is present then it is preferred at 4’ position to retain the beta2
  • If phenyl group has no phenolic substituent then it may act directly or indirectly.[2]

 

Method of synthesis

i. Bromination of 3,5-dibenzyloxyacetophenone gives 3,5-dibenzyloxybromoacetophenone.

ii. It is then reacted with N-benzyl-N-tert-butylamine to give a ketone intermediate.

iii. Intermediate undergoes reduction to give terbutaline.

 

Therapeutic Uses

The drug is used:

  • As a bronchodilator
  • Treatment of asthma
  • As a tocolytic

 Side Effects

Common side effects of terbutaline are

  • tachycardia,
  • hypotension,
  • hypokalemia,
  • hyperglycemia,
  • headache,
  • tremors,
  • anxiety and nervousness.

Less common side effect of this drug is pulmonary edema.

MCQs

Q.1 “(RS)-5-[2-(tert-Butylamino)-1-hydroxyethyl]benzene-1,3-diol” is the IUPAC nomenclature of which drug?

a) Terbutaline

b) Doxazocin

c) Methoxamine

d) Phenoxybenzamine

Q.2 Number of chiral carbons in the structure of Terbutaline is?

a) 0

b) 1

c) 2

d) 3

Q.3 Match the following with correct classifications of the drugs.

i. Terbutalin A. Aromatase inhibitors
ii. Paclitaxel B. Triazine
iii. Dacarbazine C. Taxanes
iv. Letrozole D. ß2-adrenergic agonist

 a) i-D, ii-C, iii-B, iv-A

b) i-D, ii-B, iii-A, iv-C

c) i-B, ii-C, iii-A, iv-D

d) i-C, ii-D, iii-B, iv-A

Q.4 Correct steps for the mechanism of action of the drug…..

I. Stimulation of Adenyl cyclase enzyme.

II. Relaxation in bronchial smooth muscles.

III. Conversion of ATP into CAMP increases.

a) I – II – III

b) II – I – III

c) I – III – II

d) III – II – I

Q.5   Correct sequence for True and False for the given statements related with the SAR of drug Xylometazoline.

  • When R1 is increased in size, activity of alpha receptors decreases and activity of the beta receptors increases
  • At least one of the groups is required which can form hydrogen bonds. And if only one group is present then it is preferred at 4’ position to retain the beta2 activity
  • Activity of both alpha and beta receptors is maximum when R1 is methyl group.
  • Primary or secondary aliphatic amine separated by two carbons from a substituted benzene ring is essential for the high agonist activity.

a) TTFT

b) TTTF

c) TFTF

d) TTTT

Q.6 Type of ring present in the structure of Terbutaline?

a) Benzene

b) Imidazoline

c) Both a) and b)

d) No rings are present

 Q.7 The drug that can be given for relief in bronchospasm?

a) Terbutaline

b) Vincristine

c) Fludarabine

d) Vinblastine

For More Standard and Quality Question Bank you can Join Our Test Series Programme for GPAT, NIPER JEE, Pharmacist Recruitment Exam, Drug Inspector Recruitment Exams, PhD Entrance Exam for Pharmacy

ANSWERS

1-a

2-b

3-a

4-c

5-d

6-a

7-a

 

REFERENCES

[1] Lemke TL, Zito SW, Roche VF, Williams DA. Essentials of Foye’s principles of medicinal chemistry. Wolters Kluwer; 2017, 340

[2] Lemke TL, Zito SW, Roche VF, Williams DA. Essentials of Foye’s principles of medicinal chemistry. Wolters Kluwer; 2017, 348-352

 

Leave a Reply

Your email address will not be published. Required fields are marked *

9 + 11 =

×
Free Video Lectures of Pharmacy Exams
Apply now

Developed By Connect Globes