52-67-5 Usage
Description
3,3-Dimethyl-D(-)-cysteine is an optically active form of penicillamine with D-configuration, which is a heavy metal chelator and a penicillin degradation product. It is a white to off-white crystalline powder and is used in various applications due to its chelating properties and potential therapeutic effects.
Uses
Used in Pharmaceutical Industry:
3,3-Dimethyl-D(-)-cysteine is used as a chelating agent for the treatment of heavy metal poisoning, particularly in cases of copper, mercury, and lead poisoning. It is effective in increasing urinary and fecal copper excretion and decreasing liver copper concentration, making it a drug of choice for the management of Wilson's disease, a copper-overload disease state.
Used in Treatment of Wilson's Disease:
3,3-Dimethyl-D(-)-cysteine is used as a copper chelator to form mixed disulfides with cysteine or other sulfide media components, helping in the treatment of Wilson's disease by reducing copper levels in the body.
Used in Antirheumatic Applications:
3,3-Dimethyl-D(-)-cysteine is used as an antirheumatic agent, reducing the number of T cells, inhibiting microphages by reducing the activity of Interleukin and rheumatoid factor, and preventing crosslinking of collagen.
Used in Treatment of Cystinuria and Scleroderma:
3,3-Dimethyl-D(-)-cysteine is used in the treatment of Cystinuria, a genetic disorder characterized by the accumulation of cystine crystals in the body, and Scleroderma, a connective tissue disease that causes skin and other organs to harden and tighten.
Used in Arsenic Poisoning:
3,3-Dimethyl-D(-)-cysteine is used as a chelating agent in the treatment of arsenic poisoning, helping to remove the toxic element from the body.
Brand names for formulations containing 3,3-Dimethyl-D(-)-cysteine include Cuprimine (Merck) and Depen (Medpointe).
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
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.
