Penicillamine

Therapeutic Function Used in treatment of rheumatoid arthritis Chemical Name 3-Mercapto-D-valine Common Name Dimethylcysteine 

Trade Name Manufacturer Country Year Introduced 

Potassium benzyl penicillin Mercuric chioride Hydrogen sulfide 

M Preparation of isopropyiidene peniciiiamine hydrochioride To the filtrate obtained In step (b) is added at 20°C to 25°C a total of 85 g of hydrogen sulfide. The precipitated HgS is filtered off and the filtrate is concentrated under reduced pressure to a volume of 200 to 500 ml. Following e polish filtration, the product-rich concentrate is mixed with 1.5 liters of isobutyl acetate. The mixture is refluxed at about 40 C under reduced pressure in equipment fitted with a water separation device. When no further water separates, the batch is cooled to 30t and filtered. The reactor is washed with 1 liter of acetone, which Is used also to wash the cake. The cake is further washed with 200 ml of acetone. The acetone washes are added to the isobutyl acetate filtrate and the mixture is refluxed for 20 to 30 minutes. After a holding period of one hour at 5°C, the crystals of isopropyiidene penicillamine hydrochloride are filtered and washed with 200 m of acetone. On drying for twelve hours at 25°C this product, containing 1 mol of water, weighs about 178 g (73%). 

and Sawada, J. U.S. Patent 4,150,240 April 15, 1979 assigned to Taisho Pharmaceutical Co., Ltd. (Japan) 

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P. E. Smith and B. M. Pettitt. Amino acid side-chain populations in aqueous and saline solution Bis(penicillamine) enkephalin. Biopolymers, 32 1623-1629,... 

Penetrating stains Penetration resistance Penetration theory Penetrometers Peng-Robinson equation DL-Pemcillamine Penicillamine [52-67-5]... 

Penicillamine (29) can be effective in patients with refractory RA and may delay progression of erosions, but adverse effects limit its useflilness. The most common adverse side effects for penicillamine are similar to those of parenteral gold therapy, ie, pmritic rash, protein uria, leukopenia, and thrombocytopenia. Decreased or altered taste sensation is a relatively common adverse effect for penicillamine. A monthly blood count, platelet count, and urinalysis are recommended, and also hepatic and renal function should be periodically monitored. Penicillamine is teratogenic and should not be used during pregnancy. 

Clinical trials for r-IEN-y in RA indicated that the dmg is well tolerated (52). Consistent improvement in tender and swollen joint scores was observed, but a large number of patients were needed in the trial to show statistical significance for r-IEN-y treatment. In certain individuals, responses were remarkable. An additive effect between r-IEN-y and penicillamine was detected. Efficacy was lower when r-IEN-y was combined with gold therapy. Research is continuing. 

The amino acids L-leucine, T-phenylalanine, L-tyrosine, and L-tryptophan all taste bitter, whereas their D-enantiomers taste sweet (5) (see Amino ACIDS). D-Penicillamine [52-67-5] a chelating agent used to remove heavy metals from the body, is a relatively nontoxic dmg effective in the treatment of rheumatoid arthritis, but T.-penicillamine [1113-41 -3] produces optic atrophy and subsequent blindness (6). T.-Penicillamine is roughly eight times more mutagenic than its enantiomer. Such enantioselective mutagenicity is likely due to differences in renal metaboHsm (7). (R)-ThaHdomide (3) is a sedative—hypnotic (3)-thaHdomide (4) is a teratogen (8). 

Over 250 analogues of the B vitamers have been reported (11,100). Nearly all have low vitamin B activity and some show antagonism. Among these are the 4-deshydroxy analogue, pyridoxine 4-ethers, and 4-amino-5-hydroxymeth5i-2-methyipyrimidine, a biosynthetic precursor to thiamine. StmcturaHy unrelated antagonists include dmgs such as isoniazid, cycloserine, and penicillamine, which are known to bind to pyridoxal enzyme active sites (4). 

The following trivial names have been assigned to the penicillin transformation products shown (6), benzylpenicilloate (7), benzylpenaldic acid (8), D-penicillamine (9), a-methyl D-a-benzylpenicilloate (10), benzylpenillic acid (11), benzylpenillamine (12), benzyl-isopenillic acid (13), benzylpenilloic acid (14), benzylpenilloaldehyde (15), benzylpenicil-lenic acid (16) benzylpenillonic acid methyl ester and (17), dethiobenzylpenicillin methyl ester. 

TV-Acetyl penicillamine /D- 15537-71-0, DL-59-53-0] M 191.3, m 183°, 186-187° (DL-form), 189-190° (D-form), D-form [a] +18° (c 1, 50% EtOH), pKes,(1)-3.0 (COjH), pKes,(2) 8.0 (SH). Both forms are recrystd from hot H2O. A pure sample of the D-form was obtained after five recrystns. [Crooks in The Chemistry of Penicillin Clarke, Johnson and Robinson eds, Princeton University Press, 470 7949.]... 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

Penicilloic acid 5, the substrate for the projected lactamization reaction, could be derived from the suitably protected intermediate 6. Retrosynthetic disassembly of 6, in the manner illustrated, provides D-penicillamine hydrochloride (7) and tert-butyl phthalimido-malonaldehydate (8) as potential building blocks. In the synthetic direction, it is conceivable that the thiol and amino groupings in 7 could be induced to converge upon the electrophilic aldehyde carbonyl in 8 to give thiazolidine 6 after loss of a molecule of water. 

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