Nilvadipine

Nilvadipine

Systematic (IUPAC) name
5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
ATC code	C08CA10 (WHO)
PubChem	CID: 4494
DrugBank	DB06712 Y
ChemSpider	4338 N
UNII	0214FUT37J Y
KEGG	D01908 Y
ChEMBL	CHEMBL517427 N
Chemical data
Formula	C19H19N3O6
Molecular mass	385.370 g/mol
SMILES CC1=C(C(C(=C(N1)C#N)C(=O)OC)C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OC(C)C
InChI InChI=1S/C19H19N3O6/c1-10(2)28-19(24)15-11(3)21-14(9-20)17(18(23)27-4)16(15)12-6-5-7-13(8-12)22(25)26/h5-8,10,16,21H,1-4H3 N Key:FAIIFDPAEUKBEP-UHFFFAOYSA-N N
NY (what is this?)  (verify)

Nilvadipine is a calcium channel blocker (CCB) used for the treatment of hypertension and chronic major cerebral artery occlusion.

Pathohistochemical studies have revealed that the volume of the infarction in the middle cerebral artery occlusion model could be decreased by nilvadipine.

Nilvadipine was tested in clinical trial as a possible treatment for Alzheimer's Disease in Ireland by the Roskamp Institute, Florida, USA and Trinity College, Ireland.

Following this study, an international research consortium led by Trinity College Dublin (Ireland) in May 2011 announced the selection for funding of a large-scale European clinical trial of Nilvadipine, an Alzheimer’s disease drug developed at the Roskamp Institute in Sarasota. More than 500 Alzheimer’s patients will participate in the multicenter Phase III clinical trial designed to study the effectiveness of Nilvadipine.

Synthesis

Nilvadipine synthesis: Y. Sato, BE 879263 ; idem, U.S. Patent 4,338,322 (1980, 1982 both to Fujisawa).

The product from the condensation of meta-nitrobenzaldehyde with dimethyl acetal from methyl 4-formylacetoacetate (1) provides the starting material for a dihydropyridine in which one of the methyl groups is replaced with by a nitrile. Rxn of 3 with the enamine from isopropyl acetoacetate (4) affords the corresponding dihydropyridine; hydrolysis of the ketal with aqueous acid affords the aldehyde (5). That function is then converted to the oxime (6) by reaction with hydroxylamine. Treatment of this intermediate with hot acetic acid causes the oxime to dehydrate to a nitrile. There is thus obtained nilvadipine (5).

Notes

• See for Flordipine.