Diltiazem

Title: Diltiazem
CAS Registry Number: 42399-41-7
CAS Name: (2S-cis)-3-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
Additional Names: (+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate (ester)
Molecular Formula: C22H26N2O4S
Molecular Weight: 414.52
Percent Composition: C 63.74%, H 6.32%, N 6.76%, O 15.44%, S 7.74%
Literature References: Calcium channel blocker with vasodilating activity. Prepn (unspec stereochem): H. Kugita et al., DE 1805714; eidem, US 3562257 (1969, 1971 both to Tanabe Seiyaku); eidem, Chem. Pharm. Bull. 19, 595 (1971). Resolution of optical isomers: H. Inoue et al., Yakugaku Zasshi 93, 729 (1973), C.A. 79, 66331w (1974). Stereospecific synthesis: K. Igarashi, T. Honma, DE 3415035; eidem, US 4552695 (1984, 1985 both to Shionogi). Structure-activity studies: Sato et al., Arzneim.-Forsch. 21, 1338 (1971); T. Nagao et al., Chem. Pharm. Bull. 21, 92 (1973). Pharmacology and toxicity: eidem, Jpn. J. Pharmacol. 22, 467 (1972). Metabolism: Meshi et al., Chem. Pharm. Bull. 19, 1546 (1971). Review of synthesis and pharmacology: H. Inoue, T. Nagao, Chron. Drug Discovery 3, 207-238 (1993). Comprehensive description: D. J. Mazzo et al., Anal. Profiles Drug Subs. Excip. 23, 53-98 (1994). Review of pharmacology and efficacy in angina: M. Chaffman, R. N. Brogden, Drugs 29, 387-454 (1985); in hypertension: M. R. Weir, J. Clin. Pharmacol. 35, 220-232 (1995). Comparative clinical trial in prevention of complications of hypertension: L. Hansson et al., Lancet 356, 359 (2000).
Derivative Type: Hydrochloride
CAS Registry Number: 33286-22-5
Manufacturers' Codes: CRD-401
Trademarks: Adizem (Napp); Altiazem (Lusofarmaco); Angizem (Inverni); Cardizem (Biovail); Deltazen (Sanofi-Aventis); Dilacor XR (Watson); Diladel (Polifarma); Dilpral (Orion); Dilrene (Sanofi-Aventis); Dilzem (Gecke); Dilzene (Sigma-Tau); Masdil (Esteve); Tiazac (Forest); Tildiem (Sanofi-Aventis); Zilden (Pharmacia)
Molecular Formula: C22H26N2O4S.HCl
Molecular Weight: 450.98
Percent Composition: C 58.59%, H 6.03%, N 6.21%, O 14.19%, S 7.11%, Cl 7.86%
Properties: Fine needles from ethanol-isopropanol, mp 207.5-212°. Odorless, with a bitter taste. [a]D24 +98.3 ± 1.4° (c = 1.002 in methanol). Freely sol in water, methanol, chloroform, formic acid; slightly sol in abs ethanol. Practically insol in benzene. Insol in ether. LD50 in male, female mice, male, female rats (mg/kg): 61, 58, 38, 39 i.v.; 260, 280, 520, 550 s.c.; 740, 640, 560, 610 orally (Nagao, 1972).
Melting point: mp 207.5-212°. Odorless
Optical Rotation: [a]D24 +98.3 ± 1.4° (c = 1.002 in methanol)
Toxicity data: LD50 in male, female mice, male, female rats (mg/kg): 61, 58, 38, 39 i.v.; 260, 280, 520, 550 s.c.; 740, 640, 560, 610 orally (Nagao, 1972)
Therap-Cat: Antianginal; antihypertensive; antiarrhythmic (class IV).
Keywords: Antianginal; Calcium Channel Blocker; Benzothiazepines.
Dimecrotic Acid Dimefline Dimemorfan Dimenhydrinate Dimenoxadol

Diltiazem
Diltiazem structure.svg
Diltiazem ball-and-stick.png
Systematic (IUPAC) name
cis-(+)-[2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl)
-3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9,
11-trien-4-yl]ethanoate
Clinical data
Trade names Cardizem, Dilacorxr
AHFS/Drugs.com monograph
MedlinePlus a684027
Pregnancy cat. D: (USA)
Legal status  ?
Routes Oral
Pharmacokinetic data
Bioavailability 40%
Metabolism Hepatic
Half-life 3–4.5 hours
Excretion Renal
Biliary
Lactic (in lactating females)
Identifiers
CAS number 42399-41-7 YesY
ATC code C08DB01
PubChem CID 39186
IUPHAR ligand 2526
DrugBank DB00343
ChemSpider 35850 YesY
UNII EE92BBP03H YesY
KEGG D07845 YesY
ChEBI CHEBI:101278 YesY
ChEMBL CHEMBL23 YesY
Chemical data
Formula C22H26N2O4S 
Mol. mass 414.519 g/mol
 YesY (what is this?)  (verify)

Diltiazem is a nondihydropyridine (non-DHP) member of the class of drugs known as calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. It is a benzothiazepine, which differentiates it from the other classes of non-DHP calcium channel blockers such as the phenylalkylamines.

It is also an effective preventive medication for migraine. It is a class 3 antianginal drug, and a class IV antiarrhythmic. It is a common adulterant of cocaine seized in the UK,[1] and has been found to reduce cocaine cravings in rats, indicating it may prolong the "high" (see below). It incites minimal reflex sympathetic changes. It is based upon a 1,4-thiazepine ring.

Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.