Lacidipine

Lacidipine

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Systematic (IUPAC) name
Diethyl 4-{o-[(E)-2-tert-butoxycarbonylethenyl]phenyl}-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
Trade names	Lacipil, Motens
AHFS/Drugs.com	International Drug Names
Legal status	℞ (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	~10%
Protein binding	>95%
Metabolism	Hepatic
Onset of action	30–50 min
Biological half-life	13–19 hours
Excretion	Feces (~70%)
Identifiers
CAS Number	103890-78-4
ATC code	C08CA09 (WHO)
PubChem	CID: 5311217
ChemSpider	4470736
UNII	260080034N Y
KEGG	D04657 Y
Chemical data
Formula	C26H33NO6
Molecular mass	455.543 g/mol
SMILES CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2/C=C/C(=O)OC(C)(C)C)C(=O)OCC)C)C
InChI InChI=1S/C26H33NO6/c1-8-31-24(29)21-16(3)27-17(4)22(25(30)32-9-2)23(21)19-13-11-10-12-18(19)14-15-20(28)33-26(5,6)7/h10-15,23,27H,8-9H2,1-7H3/b15-14+ Key:GKQPCPXONLDCMU-CCEZHUSRSA-N
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Lacidipine (tradenames Lacipil (GSK) or Motens (Boehringer Ingelheim)) is a calcium channel blocker. It is available as tablets containing 2 or 4 mg.

Synthesis

File:Lacidipine synthesis.svg

Lacidipine synthesis: C. Semeraro et al., DE 3529997 ; eidem, U.S. Patent 4,801,599 (1986, 1989 both to Glaxo).

The synthesis starts with the Wittig reaction of phthalaldehyde (1) with the ylide from triphenylphosphonium salt (2). The trans stereochemistry of the product (3) follows from the fact that the rxn is not carried out under salt-free conditions; selectivity for monoalkylation is probably due to steric hindrance from the newly introduced adjacent side chain to the adjacent formyl group. reaction of tat intermediate with ethyl acetoacetate and ammonia gives the dihydropyridine lacidipine (5).

Notes

File:Teludipine synthesis.svg

Teludipine synthesis: Claudio Semeraro, et al. U.S. Patent 5,162,345 (1992 to Glaxo).

Further modification of this compound depends on the allylic nature of the ring methyl groups. Thus reaction of 5 with pyridinium perbromide leads to the bromination of one groups and the formation of 6. The displacement of halogen by dimethylamine leads to the tertiary amine teludipine (7).

External links

• Motens 2 mg Summary of Product Characteristics
• Motens 4 mg Summary of Product Characteristics