52-67-5 Usage
Description
Different sources of media describe the Description of 52-67-5 differently. You can refer to the following data:
1. D-penicillamine (DPA) is a heavy metal chelator and is the drug of choice for management of Wilson’s disease, a copper-overload disease state. It may also be effective in arsenic, mercury, and lead chelation. Although the toxicity of DPA is relatively low, there are more effective and less toxic chelators, for most heavy metals, with the exception of copper.
2. Penicillamine is an orally bioavailable copper chelator and penicillin degradation product. It increases urinary and fecal copper excretion and decreases liver copper concentration in a rat model of copper overload when administered at 0.67 mmol/kg per day, but does not affect kidney, spleen, or brain copper levels. Penicillamine (100 mg/kg per day) dissolves copper-rich granules in hepatic lysosomes of Long-Evans cinnamon (LEC) rats, which spontaneously develop hepatic injury and acute hepatitis and have a mutation homologous to that of the human Wilson disease gene. Penicillamine has anticonvulsant and proconvulsant effects in mice when administered at 0.5 and 250 mg/kg, respectively, which are blocked by the nitric oxide synthase (NOS) inhibitors L-NAME and 7-nitroindazole . Formulations containing penicillamine have been used to treat Wilson disease, cystinuria, and active rheumatoid arthritis.
uses
D-Penicillamine is used as an antirheumatic to reduce the number of T cells, to inhibit microphages by reducing the activity of Interleukin and rheumatoid factor, and to prevent crosslinking of the collagen. It is used as a chelating agent in Wilson's disease.It is used mainly as chelating agent in heavy metal poisoning as in lead, mercury and copper poisoning. It is also used for therapy in progressive systemic sclerosis.
Biochem/physiol Actions
Penicillamine is a characteristic degradation product of penicillin type antibiotics. One atom of copper combines with two molecules of penicillamine. Penicillamine reduces excess cystine excretion in cystinuria. This is by disulfide interchange between penicillamine and cystine, which results in formation of a readily excreted penicillamine-cysteine disulfide. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. Penicillamine lowers IgM rheumatoid factor and depresses T-cell activity.
Mechanism of Action
Penicillamine chelates heavy metals including copper, iron, lead, and mercury, forming stable complexes that can then be excreted by the kidneys. One gram of penicillamine has the potential to combine with 200 mg of copper. When administered to patients with Wilson's disease, however, a 1 gm dose of penicillamine results in excretion of only 2 mg of copper.Penicillamine complexes with cystine, forming penicillamine-cysteine disulfide. This compound is more soluble than cysteine-cysteine disulfide (cystine), thereby reducing the levels of free urinary cystine below those considered crucial to the formation of cystine stones. Existing stones also may undergo dissolution during penicillamine therapy.Penicillamine's antirheumatic action may be due, in part, to the drug's ability to inhibit the formation of collagen. Penicillamine also appears to depress circulating levels of IgM rheumatoid factor, but, in contrast to cytotoxic immunosuppressants, the drug does not reduce the absolute levels of serum immunoglobulins. Penicillamine depresses T-cell activity but not B-cell activity.
Pharmacokinetics
Penicillamine is administered orally. The distribution of penicillamine is not well known, but it is believed to cross the placenta. Protein binding is about 80%, primarily to albumin. The drug also binds to erythrocytes and macrophages. Penicillamine appears in the plasma as free penicillamine, penicillamine disulfide, and cysteine-penicillamine disulfide. A small fraction of the dose is metabolized in the liver to s-methyl-D-penicillamine. Drug excretion is primarily renal, mainly as disulfides. One study determined that, of a total dose of penicillamine, approximately 50% was excreted in the urine and 20% in the feces. Approximately 30% of the drug remained unaccounted for. When prolonged treatment is stopped, there is a slow elimination phase lasting 4—6 days.
Side Effects
More commonFeverjoint painlesions on the face, neck, scalp, and/or trunkskin rash, hives, or itchingswollen and/or painful glandsulcers, sores, or white spots on lips or in mouthLess commonBloody or cloudy urineshortness of breath, troubled breathing, tightness in chest, or wheezingsore throat and fever with or without chillsswelling of face, feet, or lower legsunusual bleeding or bruisingunusual tiredness or weaknesshttps://www.mayoclinic.org/drugs-supplements/penicillamine-oral-route/side-effects/drg-20065377https://www.drugs.com/mtm/penicillamine.html
Reference
A. J. Dixon, J. Davies, T. L. Dormandy, E. B. Hamilton, P. J. Holt, R. M. Mason, M. Thompson, J. C. Weber, D. W. Zutshi, Synthetic D(-)penicillamine in rheumatoid arthritis. Double-blind controlled study of a high and low dosage regimen, Annals of the Rheumatic Diseases, 1975, vol. 34, pp. 416-421
V. D. Steen, T. A. Medsger, G. P. Rodnan, D-Penicillamine Therapy in Progressive Systemic Sclerosis (Scleroderma): A Retrospective Analysis, 1982, vol. 97, pp. 652-659
Chemical Properties
White to off-white crystalline powder
Uses
Different sources of media describe the Uses of 52-67-5 differently. You can refer to the following data:
1. As a Penicillin metabolite, D-(-)-Penicillamin can be used in the treatment of Wilson’s disease, Cystinuria, Scleroderma and arsenic poisoning.
2. chelating agent (Cu), antirheumatic
3. D-(-)-Penicillamin is used as an antirheumatic and as a chelating agent in Wilson′s disease. It is used as a copper chelator to form mixed disulfides with cysteine or other sulfide media components. It is used to inactivate protein-1 DNA binding and to inhibit the growth of asynchronous cultures of rabbit articular chondrocytes.
Definition
ChEBI: An optically active form of penicillamine having D-configuration. Pharmaceutical form (L-form is toxic) of chelating agent used to treat heavy metal poisoning.
Brand name
Cuprimine(Merck); Depen (Medpointe).
General Description
D-Penicillamine contains a β-lactam chemical structure.
Clinical Use
Rheumatoid arthritis, Wilson’s disease, cystinuria, lead
poisoning, chronic active hepatitis
Safety Profile
Poison by
intraperitoneal route. Moderately toxic by
subcutaneous and intravenous routes. Mildly
toxic by ingestion. An experimental
teratogen. Human systemic effects by
ingestion: agranulocytosis, dermatitis, fever,
hemorrhage, increased body temperature,
dermatitis, leukopenia, proteinuria,
thrombocytopenia. Human teratogenic
effects by an unspecified route:
developmental abnormalities of the
craniofacial areas, skin, and skin appendages,
and body wall. Experimental reproductive
effects. Questionable human carcinogen
producing leukemia. Mutation data reported.
Used in the treatment of rheumatoid
arthritis, metal poisonings, and cystinuria.
When heated to decomposition it emits very
toxic fumes of NOx and SOx. See also
MERCAPTANS.
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Sodium aurothiomalate: increased risk of
haematological toxicity
Metabolism
Penicillamine undergoes limited metabolism in the liver,
to S-methyl penicillamine.
It is mainly excreted in the urine as disulfides, along with
some S-methyl penicillamine and unchanged drug; a small
amount may be excreted in the faeces
Purification Methods
The melting point of D-(-)-penicillamine depends on the rate of heating (m 202-206o is obtained by starting at 195o and heating at 2o/minute). It is soluble in H2O and alcohols but insoluble in Et2O, CHCl3, CCl4 and hydrocarbon solvents. Purify it by dissolving it in MeOH and adding Et2O slowly. Dry it in vacuo and store it under N2. [Weight et al. Angew Chem, Int Ed (English) 14 330 1975, Cornforth in The Chemistry of Penicillin (Clarke, Johnson and Robinson eds) Princeton Univ Press, 455 1949, Review: Chain et al. Antibiotics (Oxford University Press) 2 1949, Polymorphism: Vidler J Pharm Pharmacol 28 663 1976]. The D-S-benzyl derivative has m 197-198o (from H2O), [] D 17 -20o (c 1, N NaOH), -70o (N HCl). [Beilstein 4 IV 3228.]
Check Digit Verification of cas no
The CAS Registry Mumber 52-67-5 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 2 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 52-67:
(4*5)+(3*2)+(2*6)+(1*7)=45
45 % 10 = 5
So 52-67-5 is a valid CAS Registry Number.
InChI:InChI=1/C5H11NO2S/c1-6(2)4(3-9)5(7)8/h4,9H,3H2,1-2H3,(H,7,8)
52-67-5Relevant articles and documents
-
Lodemann, Edgar
, p. 462 - 466 (1979)
d-Penicillamine is used against a variety of diseases. For many years it has been successful in treating Wilson's disease, cystinuria and heavy-metal poisonings. It also proved to be effective against rheumatoid arthritis, scleroderma, chronic active hepatitis, pulmonary fibrosis and multiple sclerosis. However, the use of d-penicillamine is still limited owing to the frequent occurrence of considerable, though generally reversible, side effects. This article deals with the history of d-penicillamine as well as the methods of its synthesis, its pharmacokinetics, effects and side effects. In addition, the significance of the stereo isomeric l-penicillamine is discussed.
Organic total synthesis method of D-penicillamine
-
Paragraph 0023; 0036-0037; 0046-0047, (2020/11/23)
The invention discloses an organic total synthesis method of D-penicillamine, which comprises the following steps: carrying out Grignard reaction on a derivative of Lserine ester and a methyl Grignardreagent to obtain a first intermediate; carrying out oxidation reaction on the first intermediate and an oxidizing agent to obtain a second intermediate; carrying out sulfonylation reaction on the second intermediate and a sulfonylation reagent to obtain a third intermediate; carrying out thiolation reaction on the third intermediate and a vulcanization reagent to obtain a fourth intermediate; and carrying out hydrolysis reaction on the fourth intermediate to obtain the D-penicillamine. The initial raw materials are cheap and easy to obtain, particularly, cheap, easy-to-obtain and high-optical-purity Lserine ester derivatives can be used as the raw materials, the whole synthetic route for preparing the Dapenem is a new organic total synthesis process route, the process is simple, the reaction condition requirement is low, no toxin is left, and the safety performance is good; the product yield and the optical purity are high; and large-scale production is easy to realize.
Immunomodulatory peptides
-
, (2014/12/12)
The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.
Novel Fluorescent Dyes and Uses Thereof
-
, (2011/02/18)
The present invention provides fluorescent dyes that are based on firefly luciferin structure. These dyes are optimally excited at shorter wavelengths and have Stokes shift of at least 50 nm. The fluorescent dyes of the invention are useful for preparation of dye-conjugates, which can be used in detection of an analyte in a sample.
