33286-22-5 Usage
Uses
Used in Cardiovascular Applications:
Diltiazem hydrochloride is used as an antianginal, antihypertensive, and anti-arrhythmic (class IV) agent for managing angina pectoris and hypertension. It increases myocardial oxygen supply by relieving coronary artery spasm and reduces myocardial oxygen demand by decreasing heart rate and reducing overload.
Used in Pharmaceutical Industry:
Diltiazem hydrochloride is used as a calcium channel blocker and vasodilator agent in the development of various pharmaceutical products, such as Cardizem (Biovail), Cartia (Andrx), Dilacor (Watson), Diltzac (Apotex), Taztia (Andrx), and Tiazac (Biovail).
Used in Peripheral Vasodilation:
Diltiazem hydrochloride is used as a peripheral vasodilator to dilate peripheral arteries and arterioles, improving blood flow and reducing blood pressure.
Used in Neutrophil Regulation:
Diltiazem hydrochloride is used as a regulator of calcium release from intracellular stores in neutrophils, which can have implications for various immune and inflammatory responses.
Used in Clinical Applications:
Diltiazem hydrochloride is used as a clinically useful antihypertensive agent, with electrophysiological properties similar to those of verapamil. It is used in clinically similar treatment conditions as an antiarrhythmic agent, although it is less potent.
Used in Drug Delivery Systems:
Diltiazem hydrochloride is used in the development of drug delivery systems, such as injections, which are clear, colorless, sterile, and nonpyrogenic solutions with a pH range of 3.7 to 4.1. These formulations provide sustained-release properties, with peak plasma levels achieved 3 to 4 hours after administration.
Originator
Herbesser,TANABE SEIYAKU,Japan,1974
Manufacturing Process
β-Diethylaminoethyl chloride is condensed with 2-(4-methoxyphenyl)-3-
hydroxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one in a first step. Then a
mixture of 1.5 grams of 2-(4-methoxyphenyl)-3-hydroxy-5-(βdimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one and 20 ml of
acetic anhydride was heated on a water bath for 5 hours. The reaction
mixture was evaporated under reduced pressure to remove acetic anhydride
and the concentrated product was poured into ice water. The resulting mixture
was made alkaline with sodium bicarbonate and extracted with chloroform.
The chloroform layer was dried and evaporated to remove the solvent. The
residue was dissolved in acetone, and an ethanol solution containing hydrogen
chloride was added thereto producing 1.53 grams of 2-(4-methoxyphenyl)3-
acetoxy-5-(β-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one
hydrochloride having a melting point from 187° to 188°C.The starting material is made by reacting 4-methoxybenzaldehyde with ethyl
chloroacetate; that product with sodium ethoxide; and that product with 2-
aminothiophenol.
Therapeutic Function
Coronary vasodilator
Biological Activity
Antihypertensive and cardioprotective agent; an inhibitor of L-type Ca 2+ channels.
Biochem/physiol Actions
Product does not compete with ATP.
Clinical Use
Calcium-channel blocker:Prophylaxis and treatment of anginaHypertension
Metabolism
Diltiazem is almost completely absorbed from the
gastrointestinal tract after oral doses, but undergoes
extensive first-pass hepatic metabolism resulting in a
bioavailability of about 40%. It is extensively metabolised
in the liver, mainly by the cytochrome P450 isoenzyme
CYP3A4; one of the metabolites, desacetyldiltiazem,
has been reported to have 25-50% of the activity of the
parent compoundAbout 2-4% of a dose is excreted in urine as unchanged
diltiazem with the remainder excreted as metabolites in
bile and urine.
Mode of action
Diltiazem Hydrochloride is a benzothiazepine calcium channel blocking agent. Diltiazem hydrochloride inhibits the transmembrane influx of extracellular calcium ions into select myocardial and vascular smooth muscle cells, causing dilatation of coronary and systemic arteries and decreasing myocardial contractility. Because of its vasodilatory activity, this agent has been shown to improve the microcirculation in some tumors, thereby potentially improving the delivery of antineoplastic agents to tumor cells.
References
1) Kraus?et al.?(1998),?Molecular mechanism of diltiazem interaction with L-type Ca2+ channels; J. Biol. Chem.,?273?27205
2) Godfraind?et al. (1986),?Calcium antagonism and calcium entry blockade; Pharmacol. Rev.,?38?321
3) Fedoryak?et al.?(2004),?Spontaneous Ca2+ oscillations in subcellular compartments of vascular smooth muscle cells rely on different Ca2+ pools; Cell Res.,?14?379
4) Ishibashi?et al. (1995),?Block of P-type Ca2+ channels in freshly dissociated rat cerebellar Purkinje neurons by diltiazem and verapamil; Brain Res.,?695?88
5) Chaffman and Bogden (1985),?Diltiazem. A review of its pharmacological properties and therapeutic efficacy; Drugs,?29?387
Check Digit Verification of cas no
The CAS Registry Mumber 33286-22-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,3,2,8 and 6 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 33286-22:
(7*3)+(6*3)+(5*2)+(4*8)+(3*6)+(2*2)+(1*2)=105
105 % 10 = 5
So 33286-22-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H26N2O4S.ClH/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;1H/t20-,21+;/m1./s1
33286-22-5Relevant articles and documents
Process for preparing diltiazem using a heterogeneous trifunctional catalyst
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Page 4, (2008/06/13)
The present invention comprises a simplified synthesis of (+)-diltiazem through IE-PdOsW wherein IE is ion-exchanger, catalyzed three-component coupling reaction and Fe3+-exchanged clay catalyzed ring opening of sulfite with 2-aminothiophenol followed by cyclization as key steps.
PROCESS FOR PREPARING DILTIAZEM USING A HETEROGENEOUS TRIFUNCTIONAL CATALYST
-
Page 7-8, (2008/06/13)
The present invention comprises a simplified synthesis of (+)-diltiazem through IE-PdOsW wherein IE is ion-exchanger, catalyzed three-component coupling reaction and Fe3+-exchanged clay catalyzed ring opening of sulfite with 2-aminothiophenol followed by cyclization as key steps.
Improved procedure for Julia-Colonna asymmetric epoxidation of α,β-unsaturated ketones: Total synthesis of diltiazem and Taxol side-chain
Adger, Brian M.,Barkley, James V.,Bergeron, Sophie,Cappi, Michael W.,Flowerdew, Benjamin E.,Jackson, Mark P.,McCague, Ray,Nugent, Thomas C.,Roberts, Stanley M.
, p. 3501 - 3507 (2007/10/03)
Poly-L-leucine catalyses the asymmetric epoxidation of enones 1-6 efficiently in a non-aqueous medium to provide the epoxy ketones 7-12 (70-91% yield; 80 to ≥95% ee). The strategy was used to make diltiazem 16 and the Taxol side chain 23 in single enantiomer form.
Process for the preparation of diltiazem
-
, (2008/06/13)
(+)-Cis-3-(acetoxy)-5-[2-(dimethylamino)-ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride is prepared by N-alkylation of (+)-cis-3-hydroxy-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one with dimethylaminoethyl chloride and K2 CO3 in toluene/water, addition of a solubilizing agent and in the presence of a phase-transfer catalyst, the toluene phase being directly subjected to the final O-- acetylation.
Process for the preparation of benzothiazepin-one derivatives
-
, (2008/06/13)
The object of the invention is a process for the preparation of the trans(-) (2R,3S) diastereoisomer of the glycidic esters of general formula: STR1 wherein a chlorohydrin of general formula: STR2 is reacted with a strong organic base in a suitable solvent and at a temperature between -10° C. and room temperature. Another object of the invention is intermediate compounds cis(+) (2S,3S) 1,5-benzothiazepin-4-one.
Controlled release pharmaceutical preparation
-
, (2008/06/13)
A controlled release pharmaceutical preparation comprising a core containing a medicinal compound and a coating layer containing a water-repellent salt and a water-insoluble and slightly water-permeable acrylic polymer having trimethylammoniumethyl group. Said preparation releases a medicinal compound in a sigmoid type dissolution pattern irrespective of the PH of a dissolution medium.
Some Applications of Isopropenyl Acetate to O-, N- and C-Acetylation
Gizur, Tibor,Harsanyi, Kalman
, p. 2365 - 2371 (2007/10/02)
New procedure for the preparation of drugs and drug intermediates (isosorbide-5-nitrate, diltiazem) and intermediates of potential drugs using isopropenyl acetate are described.
Process for the preparation of benzothiazepine derivatives
-
, (2008/06/13)
The present invention relates to a process for the preparation of benzothiazepine derivatives of general formula I STR1 wherein R stands for hydrogen and acetyl or of acid addition salts thereof in which a corresponding compound of general formula II STR2 in which R has the same meaning as above is reacted with 2-(dimethylamino)-ethyl chloride in a biphasic system of water and a non-combustible aliphatic polychlorinated hydrocarbon solvent in the presence of calcium hydroxide or of barium hydroxide. The process is advantageously performed at a temperature between 15° and the refluxing temperature of the aliphatic polychlorinated hydrocarbon solvent. The process is optionally performed in the presence of a suitable quaternary ammonium halide. In the process the amount of calcium hydroxide or barium hydroxide is advantageously 1-3 moles per 1 mole of the compound of general formula II, the amount of aliphatic polychlorinated hydrocarbon solvent is advantageously 15-40 ml and that of water 3-10 ml per g of the compound of general formula II and the ratio aliphatic chlorinated hydrocarbon solvent:water is advantageously 2:1 to 10:1.
