1 - Bepridil

Chemical Name 1-[2-(N-benzylanillno)-3-isobutoxypropyl)pyrrolidine Common Name — 

The first step involves the preparation of 1 -(3-isobutoxy-2-chloro)propyl pyrrolidine as an intermediate. 345 ml of thionyl chloride dissolved in 345 ml of chloroform are added, drop by drop, to 275 g of 1 -(3-isobutoxy-2-hydroxy)propyl pyrrolidine dissolved in 350 ml of chloroform, while maintaining the temperature at approximately 45°C. The reaction mixture is heated to reflux until gas is no longer evolved. The chloroform and the excess of thionyl chloride are removed under reduced pressure. The residue is poured on to 400 g of crushed ice. The reaction mixture is rendered alkaline with soda and the resulting mixture is extracted twice with 250 ml of diethyl ether. The combined ethereal extracts are dried over anhydrous sodium sulfate. After evaporation of the solvent the residue is distilled under reduced pressure. 220 g of product are obtained having the following properties boiling point = 96°C/3 mm, n074 = 1.4575. 

The final product is prepared as follows. 23,4 g of sodium amide is edded little by little to a solution of 92 g of N-benzylanillne in 500 ml of anhydrous xylene. The reaction mixture Is then heated at 130°-135 t for 6 hours. 

While maintaining the temperature at 110°C, 110 g of the product of the first step dissolved In 150 ml of xylene Is added and the product heated for 6 hours at 120°C. 

The Product having been allowed to cool to ambient temperature, 200 ml of cold water are added. The Organic phase is separated and extracted with an aqueous solution of hydrochloric acid. 

After twice washing with 100 ml of diethyl ether, the aqueous phase is made alkaline with 50% caustic soda solution. The liberated base is twice extracted with 150 ml of diethyl ether. After the ether has been evaporated, the residue is distilled under reduced pressure and has a boiling point of 184 C/0.1 mm, no O = i. 5538. 77 g of the pure base in the form of a viscous liquid is thus obtained. The hydrochloride, which is prepared in conventional manner, has a melting point of 128.  

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Absorption after po dosing is fairly complete. It undergoes extensive first-pass metaboHsm in the Hver and is 60% bioavailable. It is extensively bound (99%) to a -acid glycoproteins. Bepridil is almost completely metaboli2ed in the Hver. Seventeen metaboHtes have been identified but only the 4-hydroxy-A/-phenyl-bepridil has some pharmacological activity. The elimination half-life is 33—42 h (107). 

Bepridil (59) blocks the slow calcium channel and serves as an antianginal agent and a vasodilator. In its synthesis, alcohol (derived from epichlorohydrin) is converted to the corresponding chloride with thionyl chloride and displaced with the sodium salt of ]i-benzylaniline to give bepridil (59) °... 

Azaclorzine Bepridil Cinepazet Diltiazem Droprenil amine... 

Carbenicillin disodlum N-Benzylamine Antazoline HCI Beclamide Nialamide Reproterol 2-Benzylaniline Mianserin N-6enzylaniline Bepridil... 

Benzyl salicylate, 22 16 25 184 physical properties of, 22 13t Benzyl sulfone pyrolysis, 21 141 Benzyltrimethylammonium tribromide, bromination reagent, 4 344 Bepadin, molecular formula and structure, 5 97t, 118t Bepridil, 5 104... 

More recent applications comprise, for example, the identification of the binding site of 18 kDa human cardiac troponin C for the drug bepridil [36]. For this study, the unlabeled ligands were bound to selectively [13CH3-Met, Phe-d8]-labeled protein (Fig. 17.8). First, the 13CH3-Met signals of troponin C were easily identified from 13C-HSQC spectra. In a 2D NOESY spectrum with 13C-editing in one dimension, intermolecular NOEs could... 

Fig. 17.8 Intermolecular NOEs between [13CH3-Met, Phe-ds]-labeled cardiac troponin C and the drug bepridil (left panels, drug protein 1.5 1 right panels, 3.5 1). A, D methyl region of the H spectrum B, E HSQC spectra showing the 13CH3-Met signals of the protein C, F section from the NOESY spectrum with 13C-editing in one dimen-...

Bepridil has Class I antiarrhythmic properties and, like other such drugs, can induce new arrhythmias, including ventricular tachycardia/ventricular fibrillation (VTA/F). In addition, because of its ability to prolong the QT interval, bepridil can cause torsades de pointes type VT. Because of these properties, reserve bepridil for patients in whom other antianginal agents do not offer a satisfactory effect (see Warnings). P.285... 

Bepridil also inhibits fast sodium inward channels. Galcium channel blockers are classified by structure as follows Diphenylalkylamines - verapamil benzothiazepines - diltiazem dihydropyridines - amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine. 

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