42399-41-7 Usage
Description
Diltiazem is a calcium-channel blocker and vasodilator with the chemical name 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate, in which both stereocenters have the S configuration. It is used in the management of angina pectoris and hypertension due to its ability to relax blood vessels and improve blood flow.
Uses
Used in Cardiovascular Applications:
Diltiazem is used as an antihypertensive agent for the treatment of arterial hypertension. It helps in lowering blood pressure by dilating blood vessels, allowing for better blood flow and reducing the workload on the heart.
Used in Angina Pectoris Treatment:
Diltiazem is used as a vasodilator for the management of stable and non-stable angina pectoris, including after myocardial infarctions. It helps to alleviate chest pain and discomfort by improving blood flow to the heart muscle and reducing the oxygen demand of the heart.
Used in Pharmaceutical Industry:
Diltiazem is used as an active pharmaceutical ingredient in the formulation of various medications, specifically for the treatment of cardiovascular diseases such as hypertension and angina pectoris. It is available in the form of hydrochloride salt, which enhances its solubility and bioavailability.
Therapeutic Function
Coronary vasodilator
Mechanism of action
Diltiazem reduces the transmembrane influx of calcium ions into cells of cardiac muscle and smooth musculature of vessels. It causes dilation of coronary and peripheral vessels, increases coronary blood flow, and prevents development of coronary artery spasms. It lowers elevated arterial pressure and reduces tachycardia.
Clinical Use
The antiarrhythmic actions and uses of diltiazem are similar to those of verapamil.
Diltiazem is effective in controlling the ventricular
rate in patients with atrial flutter or atrial fibrillation.
Synthesis
Diltiazem, 5-[2-(diethylamino)ethyl]-cis-2,3-dihydro-3-hydroxy-2-
(4-methoxy-phenyl)-1,5-benzothiazepin-4(5H)-one (19.3.10), is synthesized in the following
manner. The condensation of 4-methoxybenzaldehyde with methylchoroacetate in the presence
of sodium methoxide in Darzens reaction conditions gives methyl ester of 3-
(4-methoxyphenyl)-glycidylic acid (19.3.5). Reacting it with 2-aminothiophenol with the
opening of epoxide ring gives methyl ester of 2-hydroxy-3-(2'-aminophenylthio)-3- (4"-
methoxyphenyl)propionic acid (19.3.6). Hydrolysis of the resulting compound with alkali
leads to the formation of the corresponding acid (19.3.7) in the form of a racemic mixture,
which when on interaction with (+)-α-phenylethylamine gives threo-(+)-2-hydroxy-3-(2'-
aminophenylthio)-3-(4"-methoxyphenylpropionic acid (19.3.8). Boiling this in a mixture of
acetic anhydride/dimethylformamide/pyridine system brings to cyclization to the thiazepine
ring and simultaneously acylates the hydroxyl group, forming (+)-cis-2-(4-methoxyphenyl)-
3-acetoxy-2,3-dihydro-1,5-benzothiazepin-4-(5H)-one (19.3.9). Alkylation of the resulting
product with 2,2-dimethylaminoethylchloride forms diltiazem (19.3.10).
Check Digit Verification of cas no
The CAS Registry Mumber 42399-41-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 4,2,3,9 and 9 respectively; the second part has 2 digits, 4 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 42399-41:
(7*4)+(6*2)+(5*3)+(4*9)+(3*9)+(2*4)+(1*1)=127
127 % 10 = 7
So 42399-41-7 is a valid CAS Registry Number.
InChI:InChI=1/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1
42399-41-7Relevant articles and documents
Crystal structures and physicochemical properties of diltiazem base and its acetylsalicylate, nicotinate and l-malate salts
Stepanovs,Jure,Gosteva,Popelis,Kiselovs,Mishnev
, p. 1235 - 1241 (2016)
Diltiazem is a drug used as a calcium channel blocker in the treatment of cardiovascular disorders. Because of the poor aqueous solubility of the drug, its hydrochloride salt has been marketed. Due to the short elimination half-life of diltiazem, extended-release formulations were developed. In the present work, the crystal engineering approach has been employed to obtain diltiazem forms with lower water solubility by treating with carboxylic acids. Three molecular salts of diltiazem with aspirin, niacin and l-malic acid were synthesized and characterized by single crystal and powder XRD, DTA, solid state CP-MAS, NMR and UV/vis techniques. The single crystal structure determination allowed us to study the supramolecular structures and proton transfer interactions from the carboxylic acids to diltiazem in the solid state, while the NMR studies showed the interactions in solution. In the crystal, the N,N-(dimethyl)ethylamine fragment of the drug molecule interacts with the carboxylic groups of the acids to form heterosynthons. The maximum 40-fold decrease of the aqueous solubility is achieved for diltiazem acetylsalicylate hydrate in comparison with the solubility of diltiazem hydrochloride.
Studies of the Resolution of Racemates in the Synthesis of Diltiazem
Gizur, Tibor,Harsanyi, Kalman,Fogassy, Elemer
, p. 628 - 631 (1994)
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Methods for predicting the response to statins
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, (2011/10/13)
The invention provides methods for optimizing therapeutic efficacy for treating hypercholesterolemia in a subject having a cardiovascular disease (CVD), comprising (a) determining subject characteristics that affect the likelihood of reaching a goal level of low density lipoprotein (LDL); and (b) obtaining success probabilities of a variety of statin treatments for reaching said goal level of LDL using said subject characteristics and a multivariate model; and (c) administrating the optimal statin treatment with the highest success probability of step (b) to said subject thereby optimizing therapeutic efficacy for treating hypercholesterolemia in said subject.