52-53-9

Basic information

• Product Name: Verapamil
• Synonyms: -2-isopropyl-;2-isopropyl-;4-dimethoxy-alpha-(1-methylethyl)-l)-;5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylv;5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylval;5-((3,4-Dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile;aleronitrile;alpha-((n-methyl-n-homoveratryl)-gamma-aminopropyl)-3,4-dimethoxyphenylaceto
• CAS NO: 52-53-9
• Molecular Formula: C₂₇H₃₈N₂O₄
• Molecular Weight: 454.6
• EINECS: 200-145-1
• Product Categories: Verapamil
• Mol File: 52-53-9.mol
• Article Data: 11

Chemical Properties

• Melting Point: 25°C
• Boiling Point: 243-246 °C (1.3 Pa)
• Flash Point: 308.3 °C
• Appearance: /
• Density: 1.1267 (rough estimate)
• Refractive Index: 1.5448
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 8.6(at 25℃)
• CAS DataBase Reference: Verapamil(CAS DataBase Reference)
• NIST Chemistry Reference: Verapamil(52-53-9)
• EPA Substance Registry System: Verapamil(52-53-9)

Safety Data

• Hazardous Substances Data: 52-53-9(Hazardous Substances Data)

Usage

Chemical Description

Verapamil is a calcium channel blocker that has been shown to increase the cellular accumulation of vincristine.

Uses

Different sources of media describe the Uses of 52-53-9 differently. You can refer to the following data:
1. Vasodilator (coronary).
2. Verapamil is primarily used as an antiarrythmic for treating ventricular arrhythmias; however, currently it is being forced out gradually by adenosine.
3. Verapamil is used for preventing angina pectoris attacks, arterial hypertension, and treating and preventing supraventricular arrhythmia (paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter, extrasystole).

Definition

ChEBI: A tertiary amino compound that is 3,4-dimethoxyphenylethylamine in which the hydrogens attached to the nitrogen are replaced by a methyl group and a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group.

General Description

Verapamil, 5-[. Hemodynamically, verapamil causesa change in the preload, afterload, contractility, heart rate,and coronary blood flow. The drug reduces systemic vascularresistance and mean blood pressure, with minor effectson cardiac output.Verapamil is a synthetic compound possessing slightstructural similarity to papaverine. It can be separated intoits optically active isomers, of which the levorotatory enantiomeris the most potent. It is absorbed rapidly after oraladministration. The drug is metabolized quickly and, as aresult, has low bioavailability. The liver is the main siteof first-pass metabolism, forming several products. Thepreferential metabolic step involves N-dealkylation, followedby O-demethylation, and subsequent conjugation ofthe product before elimination. The metabolites have no significantbiological activity. Verapamil has an eliminationhalf-life of approximately 5 hours.

Mechanism of action

Verapamil is used as an antiarrythmic drug in treating supraventricular arrythmia such as paroxysmal atrial tachycardia, and for controlling atrial fibrillation. By blocking entrance of Ca2+ in the cell, verapamil exhibits a negative inotropic effect, and therefore it cannot be combined with β-adrenoblockers or cynidine since that would lead to an increased inotropic effect.

Clinical Use

Verapamil (Isoptin, Covera), in addition to its use as an antiarrhythmic agent, has been employed extensively in the management of variant (Prinzmetal’s) angina and effort-induced angina pectoris. It selectively inhibits the voltage-gated calcium channel that is vital for action potential genesis in slowresponse myocytes, such as those found in the sinoatrial and A-V nodes. Verapamil is useful for slowing the ventricular response to atrial tachyarrhythmias, such as atrial flutter and fibrillation. Verapamil is also effective in arrhythmias supported by enhanced automaticity, such as ectopic atrial tachycardia and idiopathic left ventricular tachycardia.

Side effects

Orally administered verapamil is well tolerated by most patients. Most complaints are of constipation and gastric discomfort. Other complaints include vertigo, headache, nervousness, and pruritus.

Synthesis

Verapamil, 5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl) isopropylvaleronitrile (19.3.15), is synthesized by a scheme using 3,4- dimethoxyphenylacetonitrile as the initial substance. The synthesis of the final product (19.3.15) is accomplished by alkylating 2-(3.4-dimethoxyphenyl)-3-methylbutyronitrile (19.3.11) with N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-3-(chloropropyl)-N-methylamine (19.3.14). The initial 2-(3.4-dimethoxyphenyl)-3-methylbutyronitrile (19.3.11) is synthesized by alkylating 3,4-dimethoxyphenylacetonitrile with isopropyl chloride in the presence of sodium amide. The alkylating agent, N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-3- (chloropropyl)-N-methylamine (19.3.14), is also synthesized from 3,4-dimethoxyphenylacetonitrile followed by reduction into 3,4-dimethoxyphenylethylamine (19.3.12), with subsequent methylation into N-methyl-N-3,4-dimethoxyphenylethylamine (19.3.13). Next, the resulting N-[2-(3,4-dimethoxyphenyl)-ethyl] -N-methylamine (19.3.12) is alkylated by 1-chloro-3-bromopropane into the desired N-[2-(3,4-dimethoxyphenyl)- ethyl]-N-3-(chloropropyl)-N-methylamine (19.3.14), which is alkylated by 2-(3.4- dimethoxyphenyl)-3-methylbutyronitrile (19.3.11) to give the final product, verapamil(19.3.15).

Precautions

Verapamil must be used with extreme caution or not at all in patients who are receiving -adrenoceptor blocking agents. Normally, the negative chronotropic effect of verapamil will in part be overcome by an increase in reflex sympathetic tone. The latter is be prevented by simultaneous administration of a β-adrenoceptor blocking agent, which exaggerates the depressant effects of verapamil on heart rate, A-V node conduction, and myocardial contractility. The use of verapamil in children less than 1 year of age is controversial.

InChI:InChI=1/C27H37N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,7-8,13-16H2,1-6H3

Upstream product

• 871703-17-2 2-(3,4-dimethoxyphenyl)-2-(2-[1,3]dioxolan-2-yl-ethyl)-3-methyl-butyronitrile 
• 3490-06-0 N-methylhomoveratrylamine 
• 36770-74-8 N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine 
• 20850-49-1 2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile 
• 102201-30-9 4-(3 4-dimethoxyphenyl)-4-cyano-5-methylcapronitrile 
• 128776-24-9 2-(2-[1,3]dioxolan-2-yl-ethyl)-3-methyl-butyronitrile 
• 625-28-5 Isovaleronitrile 

Downstream Products

• 38321-02-7 dexverapamil 
• 36622-29-4 (S)-verapamil 
• 27487-66-7 D 620 
• 34245-14-2 2-(3,4-dimethoxyphenyl)-2-isopropyl-5-methylamino-pentanenitrile 
• 67018-85-3 norverapamil 
• 23313-68-0 verapamil hydrochloride 

Relevant articles and documents

A PROCESS FOR THE PREPARATION OF VERAPAMIL HYDROCHLORIDE

The present invention relates to a process for the preparation of 5-(3,4-dimethoxyphenylethyl) methyl-amino-2-(3,4-dimethoxyphenyl)-2-isopropyl valeronitrile, which is known as Verapamil. The present invention also relates to a process for improving the purity of verapamil and therefore of its hydrochloride represented as the compound of formula I, by efficient removal of the impurities formed, affording a product of purity greater than 99 %. The process of the present invention is simple, efficient, cost-effective and industrially feasible.

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

Method for treating resistant hypertension

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.