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

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

Amlodipine

IUPAC nomenclature

3-O-ethyl 5-O-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

Classification

  • Dihydropyridines
  • Calcium channel blockers

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 408.9 g/mol
2 Physical appearance Solid
3 Melting point 199-201oC
4 Solubility Slightly soluble in water
5 Octanol/water partition coefficient 3
5 Presence of ring Dihydropyridine, phenyl
6 Number of chiral centers 1

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Mechanism of Action

  • Amlodipine blocks the entry of calcium ions into vascular smooth muscles and cardiac muscles at the time of depolarization.
  • Amplodipine can bind with dihydropyridine and nondihydropyridine receptor sites present on the cell membrane.
  • There is stronger effect of this drug on vascular smooth muscles than on cardiac muscles which helps in reducing the peripheral vascular resistance, which results in lowering the blood pressure.

 

Structure Activity Relationship

General structure activity of dihydropyridines calcium channel blockers can be summarized as:

  • R1 should be unsubstituted.
  • R1 should be easily detachable group.
  • Basic amino ethyl ether chain at R2 increases the potency of drug, while H/aryl group results in loss of activity of drug.
  • Substitution of R3 and R5 with alkoxy carbonyl group gives optimum activity.
  • Branching of alkyl chain of ester group decreases the activity.
  • R4 must be phenyl ring.
  • S-enantiomers are more active than R-enantiomers.

 

Method of synthesis

i. Ethyl-4-chloroacetoacetate reacts with 3-azidoethanol in presence of sodium hydride to give ethyl-4—(2-azidoethoxy)-acetoacetate.

ii. The last reacts with 2-chlorobenzaldehyde and methyl-3-aminocrotonate to give 3-ethyl-5-methyl-2-[(-azidoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinecarboxylate.

iii. On reduction of the above formed compound, amplodipine is formed. [1]

Medicinal Uses

Amlodipine is used for the treatment of:

  • Coronary artery disease
  • Chronic stable angina
  • Vasospastic angina
  • Hypertension
  • Prevention of heart attacks 

 

Side Effects

Side effects of Amlodipine are:

  • Dizziness
  • Weakness
  • Flushing
  • Fainting
  • Lightheadedness
  • Swelling of ankles
  • Constipation
  • Headache
  • Allergic reactions 

 

 

MCQs

Q.1 “3-O-ethyl 5-O-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate” is the IUPAC nomenclature of which drug?

a) Carvedilol

b) Pentazocine

c) Amlodipine

d) Tropicamide

Q.2 Melting point of drug Amlodipine is?

a) 408.9oC

b) 199-201 oC

c) 345 oC

d) 741 oC

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

i. Amplodipine A. Narcotic antagonist
ii. Phenacemide B. Anticonvulsant
iii. Pentobarbital C. Sedative-hypnotics
iv. Nalorphine D. Calcium channel blocker

 a) i-C, ii-A, iii-D, iv-B

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

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

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

Q.4 Mechanism of action of the drug Amlodipine includes?

I. Amlodipine blocks the entry of calcium ions into vascular smooth muscles and cardiac muscles at the time of depolarization.

II. Amplodipine can bind with dihydropyridine and nondihydropyridine receptor sites present on the cell membrane.

III. There is stronger effect of this drug on vascular smooth muscles than on cardiac muscles which helps in reducing the peripheral vascular esistance, which results in lowering the blood pressure.

a) I, II, III

b) II, III

c) I, III

d) I, II

Q.5   Correct sequence for True and False for the given statements related with the SAR of Thiazide diuretics can be?

  • R1 should be unsubstituted.
  • R1 should be easily detachable group.
  • Basic amino ethyl ether chain at R2 increases the potency of drug, while H/aryl group results in loss of activity of drug

a) TFF

b) FFT

c) TTT

d) FFF

Q.6 Number of chiral carbons present in the structure of amlodipine is?

a) 0

b) 1

c) 2

d) 3

 Q.7 The drug amlodipine is mainly used for?

a) Chronic stable angina

b) Treatment of hypertesnsion

c) Treatment of vasospastic angina

d) All of the above

 

 

 

 

 

 

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ANSWERS

1-c

2-b

3-c

4-a

5-c

6-b

7-d

 

 

 

REFERENCES

 [1] Vardanyan R, Hruby V. Synthesis of essential drugs. Elsevier; 2006 Mar 10.

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