9950. Verapamil

Nomenclature

CAS number: 52-53-9
α-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile; 5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; α-isopropyl-α-[(N-methyl-N-homoveratryl)-γ-aminopropyl]-3,4-dimethoxyphenylacetonitrile; iproveratril; D-365.
C27H38N2O4; mol wt 454.60.
C 71.33%, H 8.43%, N 6.16%, O 14.08%.

Description and references

Prototype calcium antagonist; vasodilating activity resides primarily in the (S)-isomer. Both isomers inhibit the p-glycoprotein efflux pump in multidrug resistant tumor cells. Prepn: BE 615861; Dengel, US 3261859 (1962, 1966 both to Knoll). Pharmacology: H. Haas, G. Hrtfelder, Arzneim.-Forsch. 12, 549 (1962). Physical and chemical data: W. Appel, ibid. 562. Synthesis and absolute configuration of enantiomers: H. Ramuz, Helv. Chim. Acta 58, 2050 (1975). Stereospecific synthesis: L. J. Theodore, W. L. Nelson, J. Org. Chem. 52, 1309 (1987). LC-MS/MS determn of enantiomers and metabolites in plasma: M. Hedeland et al., J. Chromatogr. B 804, 303 (2004). CE analysis of metabolism: P. T. T. Ha et al., J. Chromatogr. A 1120, 94 (2006). Comprehensive description: Z. L. Chang, Anal. Profiles Drug Subs. 17, 643-674 (1988). Review of pharmacology and therapeutic use in arrhythmias: B. N. Singh et al., Drugs 25, 125-153 (1983); in hypertension: D. McTavish, E. M. Sorkin, ibid. 38, 19-76 (1989). Clinical trial of dexverapamil as adjunct to cancer chemotherapy: G. Kornek et al., Cancer 76, 1356 (1995); R. J. Motzer et al., J. Clin. Oncol. 13, 1958 (1995).

Chemical structure

Properties

Viscous, pale yellow oil, bp0.01 243-246°. nD25 1.5448. Practically insol in water. Sparingly sol in hexane; sol in benzene, ether. Freely sol in the lower alcohols, acetone, ethyl acetate, chloroform.

Derivative

Hydrochloride.

Nomenclature

CAS number: 152-11-4
Berkatens (Berk); Calan (Searle); Cardibeltin (Schwarz); Covera-HS (Searle); Dignover (Sankyo); Falicard (AWD); Flamon (Mepha); Geangin (GEA); Isoptin (Abbott); Quasar (Abbott); Securon (Abbott); Tarka (Abbott); Univer (Zeneus); Veracim (Cimex); Veramex (Sanofi-Synthelabo); Veraptin (Lagap); Verelan (Elan); Vertab (Chiesi); Zolvera (Rosemont).
C27H38N2O4.HCl; mol wt 491.06.
C 66.04%, H 8.01%, N 5.70%, O 13.03%, Cl 7.22%.

Properties

Crystals, dec 138.5-140.5° (corr). pH of 0.1% aq soln: 5.25. uv max: 232, 278 nm. Soly (mg/ml): water 83, ethanol (200 proof) 26, propylene glycol 93, ethanol (190 proof) >100, methanol >100, 2-propanol 4.6, ethyl acetate 1.0, DMF >100, methylene chloride >100, hexane 0.001. pKa 8.6. LD50 in mice, rats (mg/kg): 7.6, 16 i.v.; 68, 107 s.c.; 68, 67 i.p.; 163, 114 orally (Haas, Hrtfelder).

Derivative

(R)-Form hydrochloride.

Nomenclature

CAS number: 38176-02-2; 38321-02-7
Dexverapamil hydrochloride.

Properties

Crystals, mp 131-133°. [α]D25 +8.9° (c = 5.01 in ethanol).

Therapeutic Category

Antihypertensive; antianginal; antiarrhythmic (class IV).

Keywords

Antianginal; Antiarrhythmic; Calcium Channel Blocker; Arylalkylamines