Milverine (drug)

Milverine

Clinical data
Other names	Fenprin, Fenpyramine, Miospasm
Identifiers
IUPAC name N-(3,3-diphenylpropyl)pyridin-4-amine
CAS Number	75437-14-8
PubChem CID	71139
ChemSpider	64284
UNII	83B517YUVM
ChEBI	CHEBI:135196
ChEMBL	ChEMBL2105255
CompTox Dashboard (EPA)	DTXSID50868359
Chemical and physical data
Formula	C20H20N2
Molar mass	288.394 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC=C(C=C1)C(CCNC2=CC=NC=C2)C3=CC=CC=C3
InChI InChI=1S/C20H20N2/c1-3-7-17(8-4-1)20(18-9-5-2-6-10-18)13-16-22-19-11-14-21-15-12-19/h1-12,14-15,20H,13,16H2,(H,21,22) Key:KMZHYAUKFHLFNY-UHFFFAOYSA-N

Milverine (Fenprin, Fenpyramine, Miospasm) is a spasmolytic (antispasmodic) agent that was developed in the latter half of the 20th century. ^{[1] [2] [3]}

The therapeutic use of fenpyramin as a platelet-antiaggregating and antithrombotic as well as vasodilating and antianginous medicine was also identified. ^[4]

Milverine is a bifunctional molecule; one half of the molecule contains 3,3-Diphenylpropylamine and the other half of the molecule contains fampridine.

Synthesis

The chemical synthesis of milverine was identified. ^[5]

Milverine synthesis

Conjugate soft addition of benzene to cinnamic acid [140-10-3] (1) gives 3,3-diphenylpropionic acid [606-83-7] (2). Halogenation with thionyl chloride gives 3,3-diphenylpropionyl chloride [37089-77-3] (3). Schotten-Baumann reaction with 4-aminopyridine (Fampridine) [504-24-5] (4) gives 3,3-diphenyl-N-(4-pyridyl)propionamide [75437-13-7] (5). The last step involves reduction of the amide bond giving milverine (6), respectively.

References

1. Carpenedo F, Santi-Soncin E (May 1970). "[Spasmolytic activity of a new diphenylpropylaminic derivative, N-(4'-pyridyl)-3,3-diphenyl 1-aminopropane]". Minerva Medica (in Italian). 61 (43): 2417–24. PMID   5425728.
2. Baldi F, Ferrarini F, Balestra R, Borioni D, Longanesi A, Miglioli M (1984). "Effect of oral fenpyramine on meal-stimulated human sigmoid motility". Current Therapeutic Research. 36 (2): 267–272.
3. Fossati A, Sosio A, Pellegrini R, Frigo GM, D'Angelo L, Lecchini S, Marcoli M, Caravaggi M, Crema A (September 1986). "Milverine: in vitro and in vivo activity on the animal and human colon". Il Farmaco; Edizione Pratica. 41 (9): 279–89. PMID   3770157.
4. EP 0143082,Pellegrini R, Clavenna G, Bellani P,"Use of fenpyramin as platelet-antiaggregating, vasodilating, antithrombotic and antianginous medicine", assigned to Rbs Pharma (Roger Bellon Schoum) SpA 
5. DE 3002909,Masi P, Monopoli A, Saravalle AC, Zio C,"Method for Producing N- (4'-Pyridyl)-3,3-diphenyl-propylamine",published 31 July 1980, assigned to Italiana Schoum Sp