Probenecid

Base Information

• Chemical Name: Probenecid
• CAS No.: 57-66-9
• Deprecated CAS: 1384172-26-2
• Molecular Formula: C13H19NO4S
• Molecular Weight: 285.364
• Hs Code.: 29350090
• European Community (EC) Number: 200-344-3
• NSC Number: 757292,18786
• UN Number: 3249
• UNII: PO572Z7917
• DSSTox Substance ID: DTXSID9021188
• Nikkaji Number: J1.382J
• Wikipedia: Probenecid
• Wikidata: Q900898
• NCI Thesaurus Code: C772
• RXCUI: 8698
• Pharos Ligand ID: GH9NQFFHM3H3
• Metabolomics Workbench ID: 43274
• ChEMBL ID: CHEMBL897
• Mol file: 57-66-9.mol

Synonyms:Benecid;Benemid;Benuryl;Pro-Cid;Probecid;Probenecid;Probenecid Weimer

Chemical Property of Probenecid

Chemical Property:

• Appearance/Colour: white crystalline power
• Vapor Pressure: 1.91E-08mmHg at 25°C
• Melting Point: 194-196 °C
• Refractive Index: 1.6800 (estimate)
• Boiling Point: 438 °C at 760 mmHg
• PKA: 5.8(at 25℃)
• Flash Point: 218.7 °C
• PSA: 83.06000
• Density: 1.221 g/cm³
• LogP: 3.27630
• Storage Temp.: Store at RT
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• Water Solubility.: <0.1 g/100 mL at 20℃
• XLogP3: 3.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 285.10347926
• Heavy Atom Count: 19
• Complexity: 374
• Transport DOT Label: Poison

Purity/Quality:

99% ^*data from raw suppliers

Probenecid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-40
• Safety Statements: 36/37-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antigout Agents/Gout Suppressants
• Canonical SMILES: CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(=O)O
• Recent ClinicalTrials: Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney Transporters
• Recent EU Clinical Trials: The influence of UGT inhibition on endoxifen exposure in cancer patients treated with tamoxifen: A proof of concept study. “The PROTAM study”
• Recent NIPH Clinical Trials: Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial
• Indications: 1. For treating hyperuricemia with chronic gouty arthritis and tophi, take 2 times per day for adults with the dose of each time being 25 mg, increase the dose to 2 times per day after 1 week with 500 mg each time. Upon the administration, maintain the daily intake of water being at 2500mL to prevent the formation of kidney stones, simultaneously take alkaline urine drug if necessary. But make sure that: 1, the filtration rate of glomerular should be greater than 50~60mL/min; 2, no kidney stones or history of kidney stones; 3, non-acidic urine; 4, patients of non-taking salicylates; 5, have regular tests of blood and urine pH value, liver and kidney function as well as the uric acid levels in blood and urine; 6, adjust the dose according to the clinical and uric acid level and maintain for a long time with the minimum effective amount. 2. As an adjunct drug for antibiotic treatment; it can be combined together with different antibiotics such as penicillin, ampicillin, oxacillin, amoxicillin ortho chlorine, and nafcillin; Probenecid can be used for inhibiting the discharge of these antibiotics, increase their blood concentration and can maintain for a relative long time. The above information is edited by the lookchem of Dai Xiongfeng. When probenecid (ColBENEMID) is given in sufficient amounts, it will block the active reabsorption of uric acid in the proximal tubules following its glomerular filtration, thereby increasing the amount of urate eliminated. In contrast, low dosages of probenecid appear to compete preferentially with plasma uric acid for the proximal tubule anionic transport system and thereby block its access to this active secretory system. The uricosuric action of probenecid, however, is accounted for by the drug’s ability to inhibit the active reabsorption of filtered urate.
• Drug Interactions: When probenecid is used to elevate plasma concentrations of penicillin or other beta-lactams, or when such drugs are given to patients taking probenecid therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin or other beta-lactams, psychic disturbances have been reported. The use of salicylates antagonizes the uricosuric action of probenecid (see WARNINGS). The uricosuric action of probenecid is also antagonized by pyrazinamide. Probenecid produces an insignificant increase in free sulfonamide plasma concentrations, but a significant increase in total sulfonamide plasma levels. Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when sulfonamide and probenecid are coadministered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia. It has been reported that patients receiving probenecid require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving probenecid. The concomitant administration of probenecid increases the mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations. These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. Although the clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases a dosage of the drug in question should be made cautiously and in small increments when probenecid is being coadministered. Although specific instances of toxicity due to this potential interaction have not been observed to date, physicians should be alert to this possibility. Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances. In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate (see WARNINGS). Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.
• Uses: It is a kind of anti-gout drug. The product is organic acid, strongly fat-soluble, self-discharge from tubular secretion, very easily to be absorbed back. Therefore, in the presence of probenecid, the transfer of some organic acids in the tubular body will be inhibited, reducing the excretion of other organic acids. Thereby, it is used to treat chronic gout with being safe and effective. It has no effects on acute gout pain and inflammation and can’t be applied to acute gout. It is used for the treatment of gout, rheumatoid arthritis and other chronic diseases. pharmaceutical intermediate For the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administra An inhibitor of several ABC-transporters of the subfamily ABCC or MRP. Uricosuric drug. It is a uricosuric drug, that is, it increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.
• Description: Probenecid is insoluble in water and acidic solutions but is soluble in alkaline solutions buffered to pH 7.4. Probenecid initially was synthesized as a result of studies in the 1940s on sulfonamides that indicated the sulfonamides decreased the renal clearance of penicillin, extending the half-life of penicillin as supplies diminished. Probenecid thus was initially used—and is still indicated—for that purpose. Probenecid promotes the excretion of uric acid by inhibiting the urate anion exchange transporter (URAT 1), decreasing the reabsorption of uric acid in the proximal tubules. The overall effect is to decrease plasma uric acid concentrations, thereby decreasing the rate and extent of urate crystal deposition in joints and synovial fluids. Within the series of N-dialkylsulfamyl benzoates from which probenecid is derived, renal clearance of these compounds is decreased as the length of the N-alkyl substituents is increased. Uricosuric activity increases with increasing size of the alkyl group in the series methyl, ethyl, and propyl.
• Clinical Use: Probenecid is an effective and relatively safe agent for controlling hyperuricemia and preventing tophi deposition in tissues. Chronic administration will decrease the incidence of acute gouty attacks as well as diminish the complications usually associated with hyperuricemia, such as renal damage and tophi deposition. Probenecid is still used by some physicians to maintain high blood levels of penicillin, cephalosporin, acyclovir, and cyclosporine. It is not useful in treating acute attacks of gouty arthritis. If the total amount of uric acid excreted is greater than 800 mg/day, the urine should be alkalinized to prevent kidney stone formation and promote uric acid.

Technology Process of Probenecid

There total 10 articles about Probenecid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

p-carboxyphenylsulfonyl chloride (10130-89-9) + di-n-propylamine (142-84-7) → 4-[(dipropylamino)sulfonyl]benzoic acid (57-66-9)

Guidance literature:

In dichloromethane; at 0 - 20 ℃; for 18h;

DOI:10.1021/jm400485e

Reference yield: 92.0%

4-(hydroxymethyl)-N,N-dipropylbenzenesulfonamide (15148-72-8) → 4-[(dipropylamino)sulfonyl]benzoic acid (57-66-9)

Guidance literature:

With 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate; In dichloromethane; at 20 ℃; for 24h;

DOI:10.1021/acs.orglett.9b00054

Reference yield:

4-carboxybenzenesulfonyl fluoride (455-26-5) + di-n-propylamine (142-84-7) → 4-[(dipropylamino)sulfonyl]benzoic acid (57-66-9)

Guidance literature:

With 1,1,3,3-Tetramethyldisiloxane; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 25 ℃; for 24h; Reagent/catalyst;

DOI:10.1002/anie.202013976

upstream raw materials:

4-(aminosulfonyl)-benzoic acid

propyl bromide

p-carboxyphenylsulfonyl chloride

di-n-propylamine

Downstream raw materials:

4-dipropylsulfamoyl-N-[2-(1-tritylsulfanyl-1H-imidazol-4-yl)-ethyl]-benzamide

methyl 4-(N,N-dipropylsulfamoyl)benzoate

4-(dipropylsulfamoyl)-benzoyl chloride

5-chloro-2-({4-[(dipropylamino)sulfonyl]benzoyl}amino)benzoic acid

Refernces

Trifluoromethylation of Benzoic Acids: An Access to Aryl Trifluoromethyl Ketones

10.1021/acs.orglett.1c01720

The study presents an efficient method for the trifluoromethylation of benzoic acids using TMSCF3 (trimethylsilyl trifluoromethane) to produce aryl trifluoromethyl ketones. The reaction involves anhydrides as in situ activating reagents, with trifluoroacetic anhydride (TFAA) and 4-dimethylaminopyridine (DMAP) playing crucial roles in activating the carboxylic acids and facilitating nucleophilic addition. CsF (cesium fluoride) is used to enhance the yield of the desired products. The reaction is conducted in PhOMe (anisole) solvent under nitrogen at 120 °C for 15 hours. The study demonstrates a wide substrate scope, including various carboxylic acids with different functional groups, and shows high functional group tolerance. Notably, bioactive molecules such as adapalin, probenecid, and telmisartan can also be trifluoromethylated using this method, highlighting its potential in drug design and development. The reaction conditions are relatively mild, and the process is scalable, making it a practical and environmentally benign approach for synthesizing aryl trifluoromethyl ketones.