Rifampicin

Base Information

• Chemical Name: Rifampicin
• CAS No.: 13292-46-1
• Molecular Formula: C43H58N4O12
• Molecular Weight: 822.953
• Hs Code.: 3003.20
• Mol file: 13292-46-1.mol

Synonyms:3-[[(4-methyl-1-piperazinyl)imino]methyl]-rifamycin;3-(((4-Methyl-1-piperazinyl)imino)methyl)rifamycin SV;5,6,9,17,19,21-Hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-(N-(4-methyl-1-piperazinyl)formimidoyl)-2,7-(epoxypentadeca(1,11,13)trienimino)naphtho(2,1-b)furan-1,11(2H)-dione 21-acetate;8-(4-Methylpiperazinyliminomethyl) rifamycin SV;

Chemical Property of Rifampicin

Chemical Property:

• Appearance/Colour: Red to orange crystalline solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 183°C (dec.)
• Refractive Index: 1.613
• Boiling Point: 1004.42 °C at 760 mmHg
• PKA: 1.7, 7.9(at 25℃)
• Flash Point: 561.253 °C
• PSA: 220.15000
• Density: 1.34 g/cm³
• LogP: 4.34920
• Storage Temp.: 2-8°C
• Solubility.: chloroform: soluble50mg/mL, clear
• Water Solubility.: Soluble in DMSO or methanolSoluble in water, ethyl acetate, chloroform, methanol, tetrahydrofuran and dimethyl sulfoxide.

Purity/Quality:

98% ^*data from raw suppliers

Rifampicin-d3 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,Xi
• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-36/38
• Safety Statements: 26-36-37/39

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Description: Rifampicin is a semisynthetic derivative of rifamicin B, a macrolactam antibiotic and one of more than five antibiotics from a mixture of rifamicins A, B, C, D, and E, which is called a rifamicin complex, which is produced by actinomycetes Streptomyces mediteranei (Nocardia mediteranei). It was introduced into medical practice in 1968. Synthesis of rifampicin begins with an aqueous solution of rifamicin, which under the reaction conditions is oxidized to a new derivative of rifamicin S (32.7.4), with the intermediate formation of rifamicin O (32.7.3). Reducing the quinone structure of this product with hydrogen using a palladium on carbon catalyst gives rifamicin SV (32.7.5). The resulting product undergoes aminomethylation by a mixture of formaldehyde and pyrrolidine, giving 3-pyrrolidinomethylrifamicin SV (32.7.6). Oxidizing the resulting product with lead tetracetate to an enamine and subsequent hydrolysis with an aqueous solution of ascorbic acid gives 3-formylrifamicin SV (32.7.7). Reacting this with 1-amino-4-methylpiperazine gives the desired rifampicin (32.7.8).
• Uses: Semisynthetic antibiotic. Antibacerial (tuberculostatic) antibacterial (tuberculostatic) Rifampin is used as an antibiotic. It is a semisynthetic derivative of rifamycin B, a macrocyclic antibiotic produced by the mold Streptomyces mediterranei. Rifampin is used for the treatment of tuberculosis, brucellosis, Staphlococcus aureus, and other infectious diseases. Rifampicin is used to treat Tuberculosis and Tuberculosis-related mycobacterial infections. It is widely used as an antipruritic agent in the autoimmune cholestatic liver disease, primary biliary cirrhosis (PBC). It has been shown to cause hepatitis.
• Indications: Rifampin (300 to 450 mg daily) is very effective in relieving the pruritus of primary biliary cirrhosis, by inhibiting hepatic bile uptake and stimulating mixed-function oxidases. Liver enzymes should be monitored to detect druginduced hepatitis.
• Clinical Use: The incidence of hepatotoxicity was significantly higher when rifampin was combined with isoniazid than when either agent was combined with ethambutol. Allergic and sensitivity reactions to rifampin have been reported, but they are infrequent and usually not serious. Rifampin is a powerful inducer of hepatic cytochrome P450 oxygenases. It can markedly potentiate the actions of drugs that are inactivated by these enzymes. Examples include oral anticoagulants, barbiturates, benzodiazepines, oral hypoglycemic agents, phenytoin, and theophylline. Rifampin is also used to eradicate the carrier state in asymptomatic carriers of Neisseria meningitidis to prevent outbreaks of meningitis in high-risk areas such as military facilities. Serotyping and sensitivity tests should be performed before its use because resistance develops rapidly. However, a daily dose of 600 mg of rifampin for 4 days suffices to eradicate sensitive strains of N. meningitidis. Rifampin has also been very effective against M. leprae in experimental animals and in humans. When it is used in the treatment of leprosy, rifampin should be combined with dapsone or some other leprostatic agent to minimize the emergence of resistant strains of M. leprae. Other, nonlabeled uses of rifampin include the treatment of serious infections such as endocarditis and osteomyelitis caused by methicillin-resistant S. aureus or S. epidermidis, Legionnaires disease when resistant to erythromycin, and prophylaxis of H. influenzae induced meningitis. Rifampin occurs as an orange to reddish brown crystalline powder that is soluble in alcohol but only sparingly soluble in water. It is unstable to moisture, and a desiccant (silica gel) should be included with rifampin capsule containers. The expiration date for capsules stored in this way is 2 years. Tuberculosis (in combination with other antituberculosis agents; see Ch. 58) Leprosy (in combination with other antileprotic agents; see Ch. 57) Serious infection with multiresistant staphylococci and pneumococci (in combination with a glycopeptide) Elimination of nasopharyngeal carriage of Neisseria meningitidis and H. influenzae. Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapulmonary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection; rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis.
• Drug interactions: Potentially hazardous interactions with other drugs Anthelmintics: concentration of praziquantel reduced - avoid. Anti-arrhythmics: metabolism of disopyramide, and propafenone accelerated; concentration of dronedarone reduced - avoid. Antibacterials: reduced concentration of bedaquiline, chloramphenicol, delamanid, clarithromycin, dapsone, doxycycline, linezolid and trimethoprim and possibly tinidazole - avoid with bedaquiline; concentration increased by clarithromycin and other macrolides; increased risk of hepatotoxicity with isoniazid. Anticoagulants: reduced anticoagulant effect of coumarins; reduced concentration of apixaban, edoxaban and rivaroxaban; avoid with dabigatran. Antidepressants: concentration of vortioxetine reduced - consider increasing vortioxetine dose. Antidiabetics: reduced antidiabetic effect of linagliptin and tolbutamide; concentration of canagliflozin, nateglinide and repaglinide reduced; possibly reduced antidiabetic effect with sulphonylureas. Antiepileptics: reduced concentration of brivaracetam, fosphenytoin, phenytoin and lamotrigine; concentration possibly reduced by phenobarbital. Antifungals: concentration of both drugs may be reduced with ketoconazole; reduced concentration of fluconazole, itraconazole, posaconazole and terbinafine - avoid with itraconazole; concentration of isavuconazole and voriconazole reduced - avoid; initially increases then reduces caspofungin concentration. Antimalarials: avoid with piperaquine with artenimol; concentration of mefloquine reduced - avoid, concentration of quinine reduced. Antimuscarinics: concentration of active metabolite of fesoterodine reduced - avoid. Antipsychotics: reduced concentration of haloperidol, aripiprazole and clozapine - increase dose of aripiprazole; concentration of lurasidone reduced - avoid. Antivirals: concentration of abacavir, dasabuvir, ombitasvir, paritaprevir, ritonavir and tipranavir possibly reduced - avoid with dasabuvir, ombitasvir, paritaprevir and tipranavir; concentration of atazanavir, boceprevir, daclatasvir, darunavir, etravirine, fosamprenavir, indinavir, lopinavir, nevirapine, ombitasvir, rilpivirine, saquinavir,simeprevir and telaprevir reduced also risk of hepatotoxicity with saquinavir - avoid; concentration of efavirenz, maraviroc and raltegravir reduced - increase dose of efavirenz and possibly maraviroc and raltegravir; avoid with elvitegravir, ledipasvir, sofosbuvir and zidovudine; concentration of dolutegravir reduced. Apremilast: concentration of apremilast reduced - avoid. Atovaquone: concentration of atovaquone reduced (possible therapeutic failure of atovaquone); concentration of rifampicin increased - avoid. Bosentan: reduced bosentan concentration - avoid. Calcium-channel blockers: metabolism of diltiazem, verapamil, isradipine, nicardipine, nifedipine and nimodipine accelerated. Cannabis extract: concentration of cannabis extract reduced - avoid. Ciclosporin: markedly reduced levels (danger of transplant rejection); ciclosporin dose may need increasing 5-fold or more. Cobicistat: concentration of cobicistat possibly reduced - adjust cobicistat dose. Corticosteroids: reduced level of corticosteroids - double steroid dose. Give as twice daily dosage. Cytotoxics: reduced concentration of axitinib, brentuximab, bortezomib, bosutinib, cabazitaxel, cabozantinib, ceritinib, crizotinib, dabrafenib, dasatinib, everolimus, gefitinib, ibrutinib, idelalisib, imatinib, lapatinib, nilotinib, nintedanib, olaparib, osimertinib, panobinostat, ponatinib, regorafenib, vandetanib, vemurafenib, vinflunine and vismodegib - avoid; concentration of afatinib, erlotinib, ruxolitinib, sorafenib, sunitinib and trabectedin and possibly eribulin and pazopanib reduced; concentration of everolimus reduced - avoid or increase everolimus dose; active metabolite of temsirolimus reduced - avoid. Diuretics: concentration of eplerenone reduced - avoid. Guanfacine: concentration of guanfacine reduced - increase dose of guanfacine. Hormone antagonists: concentration of abiraterone reduced - avoid; concentration of tamoxifen and possibly exemestane reduced. Ivacaftor: concentration of ivacaftor reduced - avoid. Macitentan: concentration of macitentan reduced - avoid. Mycophenolate: concentration of active mycophenolate metabolite reduced. Naloxegol: concentration of naloxegol reduced - avoid. Netupitant: concentration of netupitant reduced - avoid. Oestrogens and progestogens: reduced contraceptive effect due to increased metabolism. Ranolazine: concentration of ranolazine reduced - avoid. Roflumilast: effects of roflumilast inhibited - avoid. Sirolimus: reduced sirolimus concentration. Tacrolimus: reduced tacrolimus concentration. Tadalafil: concentration of tadalafil reduced - avoid. Ticagrelor: concentration of ticagrelor reduced. Ulipristal: contraceptive effect possibly reduced - avoid.

Technology Process of Rifampicin

There total 18 articles about Rifampicin 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: 97.87%

N-amino-N'-methylpiperazine (6928-85-4) + N-tert-1,3-oxazine(5,6-c)rifamycin → rifampicin (13292-46-1)

Guidance literature:

With acetic acid; In butan-1-ol; at 70 ℃; for 2h; Temperature; Solvent; Large scale;

Reference yield: 95.5%

→ rifampicin (13292-46-1)

Guidance literature:

Reference yield:

N-amino-N'-methylpiperazine (6928-85-4) + (PhCH2)(p-(rifamycin SV-3-yl-CH=NNHCH2)C6H4CH2)N-PEGA 1900 resin → rifampicin (13292-46-1)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; at 20 ℃; for 24h;

DOI:10.1021/ol048610h

upstream raw materials:

N-amino-N'-methylpiperazine

3-formylrifamycin SV

3-[(4-methyl-piperazin-1-ylimino)-methyl]-O¹,O⁴-didehydro-rifamycin

pyrrolidine

Downstream raw materials:

C₄₅H₅₅ClN₂O₁₂

C₄₅H₅₅ClN₂O₁₂

C₄₅H₅₅FN₂O₁₂

C₄₅H₅₅FN₂O₁₂

Refernces

• 1、 Zhu, Mingzhao,Ruijter, Eelco,Wessjohann, Ludger A.. "New scavenger resin for the reversible linking and monoprotection of functionalized aromatic aldehydes". . p. 3921 - 3924. Retrieved 2004.
• 2、 -. "Process method for synthesizing rifampicin". Paragraph 0059; 0063-0065; 0069-0071; 0075-0077; 0081-0082. . Retrieved 2020/11/24.
• 3、 -. "Method for preparing rifampicin by utilizing cascade reaction of kettle type reaction device and microchannel reaction device". Paragraph 0033; 0034; 0043; 0044; 0051-0062; 0065-0068. . Retrieved 2017/08/28.