(RS)-3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.
- Calcium channel blockers
|S. NO.||PHYSICAL AND CHEMICAL PROPERTIES|
|1||Molecular weight||384.2 g/mol|
|5||Octanol/water partition coefficient||3.86|
|5||Presence of ring||Dihydropyridine, phenyl|
|6||Number of chiral centers||1|
Mechanism of Action
- The influx of calcium ions through voltage gated L-type calcium channels is inhibited by Felodipine which results in decrease in the arterial smooth muscle contractility and subsequent vasoconstriction.
- This inhibition results in overall decrease in 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. Methylacetoacetate reacts with 2,3-dichlorobenzaldehyde to give methyl-2-(2,3-dichlorobenzyidene)-acetoacetate.
ii. The last is reacted with ethylacetoacetate in presence of ammonia to give felodipine. 
Felodipine is used for the treatment of:
- Mild hypertension
- Moderate hypertension
Side effects of felodipine are:
- Swelling of ankles
- Stomach upset
- Allergic reactions
Q.1 What can be the correct IUPAC nomenclature of Felodipine?
d) (RS)-3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Q.2 Which amongst the following statements is/are correct related to the SAR of Dihydropyridines calcium channel blockers?
I. Branching of alkyl chain of ester group decreases the activity.
II. R4 must be phenyl ring.
III. S-enantiomers are more active than R-enantiomers.
a) I, III
b) II, III
c) I, II
d) I, II, III
Q.3 The correct order for the synthesis of drug Felodipine from Methyl acetoacetate can be?
I. Reaction with 2,3-dichlorobenzaldehyde
III. Reaction with ammonia
IV. Reaction with ethylacetoacetate
a) I – IV
b) I – II
c) III – II
d) I – IV – III
Q.4 Side effects of drug Felodipine is/are?
c) Muscle spasms
d) All of the above
Q.5 Match the following drugs with their correct Octanol water partition coefficient-
|i. Felodipine||A. 2.05|
|ii. Pantaprazole||B. 1.9|
|iii. Omeprazole||C. 3.86|
|iv. Polythiazide||D. 2.23|
a) i-C, ii-B, iii-A, iv-D
b) i-C, ii-A, iii-D, iv-B
c) i-A, ii-D, iii-C, iv-B
d) i-A, ii-C, iii-B, iv-D
Q.6 An example of drug from class calcium channel blockers?
Q.7 The type of ring system found in the structure of drug Felodipine is?
REFERENCES EP 311 582 (Hässle; appl. 22.9.1988; S-prior. 8.10.1987).