demeclocycline Chemical Properties

Melting point:

176°C (rough estimate)

Boiling point:

787.1±60.0 °C(Predicted)

Density 

1.3118 (rough estimate)

refractive index 

1.6000 (estimate)

solubility 

H2O:1.5(Max Conc. mg/mL);3.23(Max Conc. mM)

pka

4.50±1.00(Predicted)

Water Solubility 

1.4g/L(25 ºC)

Safety Information

Hazardous Substances Data

127-33-3(Hazardous Substances Data)

demeclocycline Usage And Synthesis

Description

Demethylchlortetracycline was isolated from the culture broth of a mutant of Streptomyces aureofaciens, the chlortetracycline-producing strain, by Lederle Research Laboratories in 1957. It shows one and one-half to two times as much in vitro antimicrobial activity and in vivo protective effect as tetracycline. Its base and hydrochloride have been used orally and by topical application to treat infections caused by Staphylococcus, Streptococcus, Rickettsia, Chlamydiae, Neisseria, Klebsiella, Proteus, Escherichia coli, and Haemophilus influenzae.

Originator

Declomycin,Lederle,US,1959

Uses

Demeclocycline, a chlortetracycline analogue produced by a mutagenised strain of Streptomyces aureofaciens, was first isolated in 1957. Like all tetracyclines, demeclocycline shows broad spectrum antibacterial and antiprotozoan activity and acts by binding to the 30S and 50S ribosomal subunits, blocking protein synthesis. Demeclocycline has been extensively cited in the literature with over 800 references relating almost exclusively to in vivo use.

Definition

ChEBI: Tetracycline which lacks the methyl substituent at position 7 and in which the hydrogen para- to the phenolic hydroxy group is substituted by chlorine. Like tetracycline, it is an antibiotic, but being excreted more slowly, effective blood lev ls are maintained for longer. It is used (mainly as the hydrochloride) for the treatment of Lyme disease, acne and bronchitis, as well as for hyponatraemia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) w ere fluid restriction alone has been ineffective.

Manufacturing Process

According to US Patent 2,878,289, a suitable medium for the preparation of inocula for the fermentation may be prepared with the following substances.
The pH of the medium thus prepared is about 6.8. An 8 ml portion is measured into an 8 inch Brewer tube and sterilized at 120°C for 20 minutes. The sterilized medium is then inoculated with 0.5 ml of an aqueous spore suspension of a strain of S. aureofaciens capable of producing chlorodemethyltetracycline, such as S-604, containing approximately 40-60 million spores per milliliter. The inoculated medium is incubated for 24 hours at 28°C on a reciprocating shaker operated at 110 cycles per minute.
A suitable fermentation medium contains water and a source of assimilable carbon and nitrogen and essential mineral salts. A typical medium suitable for production of chlorodemethyltetracycline is as follows:
A suitable fermentation medium contains water and a source of assimilable carbon and nitrogen and essential mineral salts. A typical medium suitable for production of chlorodemethyltetracycline is as follows:
Ten percent of the resulting inoculum is then transferred to a 250 ml Erlenmeyer flask containing 50 ml of the medium employed above and the flask agitated a further 72 hours under the same conditions. One ml of the resulting inoculum is then employed for the inoculation of 10 ml of an aqueous medium containing, per 1,000 ml, 30 grams extraction process soybean meal, 1 gram sodium chloride, 50 grams glucose and 7 grams calcium carbonate, in a 1" x 6" test tube.
In addition, 1 mg of sterile S-2-hydroxyethyl-DL-homocysteine is added to the tube and the tube is shaken on a rotary shaker at 280 cycles per minute at 25°C for seven days. The contents of the tube were then acidified to pH 2 by the addition of sulfuric acid and centrifuged. Examination of the supernatant liquid by paper chromatography employing the methods of Bohonos et al, Antibiotics Annual (1953-4, page 49),demonstrates the presence of 7-chloro6-demethyltetracycline,7-chlorotetracycline and tetracycline.

brand name

Declomycin (Lederle).

Therapeutic Function

Antibacterial

Safety Profile

Poison by intravenous and intraperitoneal routes. Human systemic effects by ingestion: diabetes insipidus, urine volume increase, other changes in urine composition, dermatitis, changes in the nails, allergic rhinitis, serum sickness, effects on cyclic nucleotides. Human reproductive effects by an unspecified route: postnatal measures or effects on newborn. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx.

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