Девапамил

Description

Devapamil (Devapamil, D 888, desmethoxyverapamil) is a synthetic calcium channel blocker of the phenylalkylamine (PAA) class, a research analogue of verapamil. CAS 92302-55-1, chemical formula C26H36N2O3, molecular weight 424.585, exact weight 424.58. IUPAC name: (RS)-2-(3,4-dimethoxyphenyl)-2-isopropyl-5-[2-(3-methoxyphenyl)ethylmethylamino]pentanenitrile.

Substance class and mechanism of action

Phenylalkylamine (PAA) blocker of voltage-dependent L-type calcium channels. It differs from verapamil in the absence of one methoxy group. Blocks the channel in two ways: binding in the resting state and depolarization of the membrane during sodium-potassium exchange; The affinity of devapamil for the channel at rest is tens of nanomoles, and when the channel is depolarized, the affinity increases approximately 5 times. The binding sites are localized in the internal pore of L-channels; mutation of three residues near the selective filter reduces the affinity of devapamil by approximately 100-fold.

Basic Attributes

• PSA characteristics: 54.7; XLogP3: 4.08

Physico-chemical characteristics

• Density: 1.0±0.1 g/cm3
• Boiling point: 567.0±50.0 °C at 760 mm Hg. Art.
• Flash point: 296.7±30.1°C
• Refractive index: 1.530

Application and purpose

Research reagent in electrophysiology and pharmacology of calcium channels: used to study the kinetics of binding of phenylalkylamines to L-channels, mapping binding sites in the internal pore of the channel and mechanisms of state-dependent blocking. As an analogue of verapamil without one methoxy group, devapamil serves as a tool for the comparative study of structure-activity relationships among phenylalkylamine calcium channel blockers.

Storage

Store in an airtight container in a cool, dry place, protected from light, as a reagent for laboratory and pharmacological research use.

Additionally

Synonyms: D 888, (±)-Devapamil, desmethoxyverapamil, additional CAS 102268-75-7. The compound was synthesized as an analytical tool for separating the effects of methoxy substitution on the affinity and kinetics of L-channel blocking in a series of verapamil-like phenylalkylamines.

Comparison with verapamil

The loss of one methoxy group compared to verapamil reduces lipophilicity and changes the kinetics of binding to the receptor without fundamentally changing the pharmacophore core of phenylalkylamines, which makes the verapamil/devapamil pair a convenient model for quantifying the contribution of individual substituents to the affinity and selectivity of the blocker with respect to channel states.

Identification

The synonym D 888 is used in original electrophysiological work along with the international nonproprietary designation devapamil; The racemic mixture of enantiomers is designated (±)-Devapamil.

Transportation

There are no specific UN transport codes for the reagent; transported in a sealed container as a regular laboratory chemical.