64-73-3 Usage
Description
Demeclocycline hydrochloride is a semi-synthetic tetracycline antibiotic that is produced by a genetically altered strain of Streptomyces aureofaciens. It is characterized by the absence of the C-6-methyl group found in tetracycline, which makes it more chemically stable against dehydration. Demeclocycline hydrochloride is a salt prepared from demeclocycline, taking advantage of the basic dimethylamino group that readily forms a salt in hydrochloric acid solutions. This hydrochloride form is the preferred formulation for pharmaceutical applications due to its broad-spectrum antibacterial and antiprotozoan activity.
Uses
Used in Pharmaceutical Industry:
Demeclocycline hydrochloride is used as an antibiotic for treating various bacterial infections. Its chemical stability and slower excretion rate compared to tetracycline allow it to maintain effective blood levels for longer periods, making it a suitable choice for extended treatment courses.
Demeclocycline hydrochloride is used as an antiprotozoan agent for combating infections caused by protozoan parasites. Its ability to bind to the 30S and 50S ribosomal subunits and block protein synthesis makes it effective against a wide range of protozoan species.
Additionally, Demeclocycline hydrochloride is used as a treatment for dose-dependent, reversible diabetes insipidus when used for extended periods. Its association with phototoxicity also makes it a potential candidate for research and development in the field of photodynamic therapy.
Therapeutic Function
Antibacterial
Antimicrobial activity
Occasional strains of viridans streptococci,
N. gonorrhoeae and H. influenzae are more susceptible than to tetracycline.
It is the most active tetracycline against Brucella spp.
Pharmaceutical Applications
6-Demethyl-7-chlortetracycline. A fermentation product of a
mutant strain of Streptomyces aureofaciens formulated as the
hydrochloride for oral administration.
Biochem/physiol Actions
Used to study mechanisms of bacterial protein synthesis inhibition at the level of the 30S subunit and aminoacy-tRNA A-site binding.
Pharmacokinetics
Oral absorption： 60–70%
Cmax 300 mg oral：2 mg/L after 3–6 h
Plasma half-life：c.12 h
Volume of distribution：c.1.7 L/kg
Plasma protein binding：90%
Absorption
It is promptly yet incompletely absorbed by mouth, giving
mean peak plasma levels after a single dose that are slightly
higher than those produced by oxytetracycline and chlortetracycline,
but lower than those achieved by tetracycline.
However, with repeat dosing, steady-state concentrations
exceed those for tetracycline. Simultaneous administration of
antacids markedly depresses blood levels.
Distribution and excretion
It is widely distributed, achieving concentrations in pleural
exudates
similar to those of blood. CSF penetration is
poor, especially in the absence of inflammation. Biliary
concentrations
are 20–30 times higher than those of plasma, and 40–50% of the drug can be recovered from feces. The
other route of elimination is via glomerular filtration without
reabsorption and accumulation occurs in renal failure.
Clinical Use
It has been extensively used in the management of the syndrome
of inappropriate ADH secretion in a dose of at least
1.2 g per day; therapeutic response may take several days, but
is superior to that of lithium. It has also found occasional use
in patients with water retention as a result of congestive cardiac
failure and in those with alcoholic cirrhosis and water
and electrolyte retention.
Side effects
Untoward reactions, notably gastrointestinal intolerance,
are generally those typical of the group. Occasional
patients develop transient steatorrhea.
Of particular note is the occurrence of nephrogenic diabetes
insipidus with development of vasopressin-resistant polyuria.
The effect is dose dependent and occurs with daily doses
in excess of 1.2 g. The drug inhibits activation of adenylate
cyclase and protein kinase, which are both important in the
interaction of antidiuretic hormone (ADH) with receptors
within the renal tubule, thus decreasing the effect of ADH on
the kidney. As a result, it has found a place in the treatment of
inappropriate ADH secretion.
Renal failure may occur, particularly if prescribed for those
with advanced liver cirrhosis. The mechanism is uncertain but
may in part be related to the antianabolic effect of the tetracyclines
as well as a direct toxic effect.
Photosensitivity may be severe and accompanied by vesiculation,
edema and onycholysis. It is largely restricted to exposed
skin; patients should avoid prolonged exposure to sunlight.
Synthesis
Demeclocycline, 7-chloro-4-dimethylamino-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahdroxy-1,11-dioxo-2-napthacencarboxamide (32.3.4), is produced
by a mutant strain of S. aureofaciens, in which the mechanism of transferring methyl groups
is disrupted, and thus demeclocycline or demethylchlorotetracycline differs from chlorotetracycline, oxytetracycline, and tetracycline in the absence of a methyl group at C6 of the
hydronaphthacene system. As a result, an antibiotic is synthesized that is more resistant to
acids and bases in comparison with the methyl homologs.
Drug interactions
Potentially hazardous interactions with other drugsAnticoagulants: possibly enhanced anticoagulant
effect of coumarins and phenindione.Oestrogens: possibly reduced contraceptive effects of
oestrogens (risk probably small).Retinoids: possible increased risk of benign
intracranial hypertension, avoid.
Metabolism
Demeclocycline hydrochloride, like other tetracyclines,
is concentrated in the liver, where it is metabolised
and excreted into the bile. It is found in much higher
concentrations in the bile compared with the blood.
Following a single 150 mg dose of demeclocycline
hydrochloride in normal volunteers, 44% (n = 8) was
excreted in urine and 13% and 46%, respectively, were
excreted in faeces in two patients within 96 hours as
active drug.
Purification Methods
Crystallise the salt from EtOH/Et2O or H2O and dry it in air [McCormick et al. J Am Chem Soc 79 4561 1957, Dobrynin et al. Tetrahedron Lett 901 1962]. [Beilstein 14 IV 2625.]
Check Digit Verification of cas no
The CAS Registry Mumber 64-73-3 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 4 respectively; the second part has 2 digits, 7 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 64-73:
(4*6)+(3*4)+(2*7)+(1*3)=53
53 % 10 = 3
So 64-73-3 is a valid CAS Registry Number.
InChI:InChI=1/C21H21ClN2O8.ClH/c1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31;/h3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31);1H/t6?,7?,14?,15-,21?;/m0./s1
