33286-22-5 Usage
Description
Diltiazem HCl (33286-22-5) is a?non-dihydropyridine-type blocker of L-type Ca2+ channels.1,2 Reduces Ca2+ oscillations in subcellular compartments in vascular smooth muscle cells.3?Also blocks P-type Ca2+ channels in freshly dissociated rat cerebellar Purkinje neurons.4 Clinically useful antihypertensive agent.5?Cell permeable.
Chemical Properties
Diltiazem hydrochloride is a white to off-white crystalline powder with a bitter taste. It is soluble in water, methanol, and chloroform. It has a molecular weight of 450.98. Diltiazem hydrochloride injection is a clear, colorless, sterile, nonpyrogenic solution. It has a pH range of 3.7 to 4.1.
Originator
Herbesser,TANABE SEIYAKU,Japan,1974
Uses
Different sources of media describe the Uses of 33286-22-5 differently. You can refer to the following data:
1. Diltiazem Hydrochloride is a calcium channel blocker with vasodilating activity. Anti-anginal; anti-hypertensive; anti-arrhythmic (class IV).
2. antihypertensive, sedative, antibacterial
3. Peripheral Vasodilator
4. An antianginal, antihypertensive. Regulates Calcium release from intracellular stores in neutrophils
Definition
ChEBI: Diltiazem hydrochloride is a hydrochloride salt resulting from the reaction of equimolar amounts of diltiazem and hydrogen chloride. A calcium-channel blocker and vasodilator, it is used in the management of angina pectoris and hypertension. It has a role as an antihypertensive agent, a vasodilator agent and a calcium channel blocker. It contains a diltiazem(1+). It is an enantiomer of an ent-diltiazem hydrochloride.
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.
Brand name
Cardizem (Biovail); Cartia (Andrx); Dilacor (Watson); Diltzac (Apotex); Taztia (Andrx); Tiazac (Biovail).
Therapeutic Function
Coronary vasodilator
General Description
Diltiazem hydrochloride is a calcium ion cellular influx inhibitor. It was developed and introduced inJapan as a cardiovascular agent to treat angina pectoris. Itwas observed to dilate peripheral arteries and arterioles. Thedrug increases myocardial oxygen supply by relieving coronaryartery spasm and reduces myocardial oxygen demandby decreasing heart rate and reducing overload. Diltiazemhydrochloride is used in patients with variant angina. Thedrug has electrophysiological properties similar to those ofverapamil and is used in clinically similar treatment conditionsas an antiarrhythmic agent, but it is less potent.The drug is absorbed rapidly and almost completely fromthe digestive tract. It reaches peak plasma levels within 1hour after administration in gelatin capsules. Oral formulationson the market are sustained-release preparations providingpeak plasma levels 3 to 4 hours after administration.
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 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 benzothiazepin-one derivatives
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, (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.
