Clarithromycin

Base Information

• Chemical Name: Clarithromycin
• CAS No.: 81103-11-9
• Molecular Formula: C38H69NO13
• Molecular Weight: 747.965
• Hs Code.: 29419000
• European Community (EC) Number: 617-200-4,658-034-2
• NSC Number: 758704
• UNII: H1250JIK0A
• DSSTox Substance ID: DTXSID3022829
• Nikkaji Number: J134.033F
• Wikipedia: Clarithromycin
• Wikidata: Q118551
• NCI Thesaurus Code: C1054
• RXCUI: 21212
• Metabolomics Workbench ID: 21286
• ChEMBL ID: CHEMBL1741
• Mol file: 81103-11-9.mol

Synonyms:6-O-Methylerythromycin;A 56268;A-56268;A56268;Biaxin;Clarithromycin;TE 031;TE-031;TE031

Chemical Property of Clarithromycin

Chemical Property:

• Appearance/Colour: Colourless crystalline needles
• Vapor Pressure: 5.06E-30mmHg at 25°C
• Melting Point: 217-220 °C
• Refractive Index: -92 ° (C=1, CHCl3)
• Boiling Point: 805.478 °C at 760 mmHg
• PKA: pKa 8.99(H2O t=25.0 I=0.167) (Uncertain)
• Flash Point: 440.937 °C
• PSA: 182.91000
• Density: 1.184 g/cm³
• LogP: 2.43970
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO
• Water Solubility.: 99.48mg/L(20 oC)
• XLogP3: 3.2
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 8
• Exact Mass: 747.47689126
• Heavy Atom Count: 52
• Complexity: 1190

Purity/Quality:

Above 99% ^*data from raw suppliers

Clarithromycin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn， Xi
• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 26-36-60

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CCC1C(C(C(C(=O)C(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
• Isomeric SMILES: CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
• Recent ClinicalTrials: Recurrence Rate Comparison Between Esomeprazole and Lansoprazole in Eradicating Helicobacter Pylori Infection Among Children
• Recent EU Clinical Trials: A RANDOMIZED CLINICAL TRIAL OF ORAL CLARITHROMYCIN IN COMMUNITY-ACQUIRED PNEUMONIA TO ATTENUATE INFLAMMATORY RESPONSES AND IMPROVE OUTCOMES (THE ACCESS TRIAL)
• Recent NIPH Clinical Trials: CAM (Clarithromycin) Effectivity for COVID-19 pneumonia which does not require oxygen administration; multicenter, randomized-controlled, open-label, 3-armed parallel group comparison, exploratory trial
• Chemical Structure: Clarithromycin, derived from erythromycin, contains a 14-membered macrocyclic lactone ring, similar to erythromycin and roxithromycin. In contrast, azithromycin contains a 15-membered macrocyclic ring.
• Mechanism of Action: Clarithromycin binds to the 50S bacterial ribosomal subunit of H. pylori, inhibiting protein synthesis and exerting a bacteriostatic effect. Resistance to clarithromycin arises from specific point mutations in the peptidyl transferase region of the bacterial 23S ribosomal RNA.
• Indications and Usage: Clarithromycin is a macrolide antibiotic commonly used to treat atypical pneumonia and infections caused by Helicobacter pylori. It acts as a strong inhibitor of the hepatic statin uptake transporters OATP1B1 and OATP1B3.
• Treatment of Helicobacter pylori Infections: Helicobacter pylori is a bacteria responsible for gastric conditions like gastritis, peptic ulcers, and gastric carcinoma. Clarithromycin has been a key component of H. pylori treatment due to its low minimal inhibitory concentration (MIC) and good mucosal diffusion. However, the efficacy of triple therapy involving clarithromycin is declining due to bacterial resistance.
• Antibiotic Resistance: Resistance to clarithromycin in H. pylori is caused by specific mutations in the 23S ribosomal RNA. This antibiotic resistance is recognized as a global health issue by organizations like the World Health Organization (WHO).
• Clinical Considerations: Clinicians must carefully manage drug interactions and antibiotic resistance when prescribing clarithromycin, particularly in the context of H. pylori eradication and concurrent statin therapy.
• Drug-Drug Interactions: Clarithromycin interacts with statins, affecting their metabolism. Strategies to manage these interactions include avoiding co-administration of certain statins (atorvastatin, lovastatin, simvastatin), considering dose adjustments or alternative antibiotics for other statins (pitavastatin, pravastatin), and cautious use of pravastatin with dose limitation.

Technology Process of Clarithromycin

There total 30 articles about Clarithromycin 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: 96.0%

6-O-methylerythromycin A N-oxide (118074-07-0) → clarithromycin (81103-11-9)

Guidance literature:

6-O-methylerythromycin A N-oxide; With tin(ll) chloride; In isopropyl alcohol; at 30 - 40 ℃; for 2h;

With sodium hydrogencarbonate; In water; isopropyl alcohol;

Reference yield: 95.0%

clarythromycin 9-O-(2-pyrimidyl)oxime (930287-49-3) → clarithromycin (81103-11-9)

Guidance literature:

With sodium hydrogensulfite; In ethanol; water; at 80 ℃; for 6h;

DOI:10.1016/j.tetlet.2006.12.124

Reference yield: 92.0%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + 6-O-methylerythromycin A N-oxide (118074-07-0) → clarithromycin (81103-11-9)

Guidance literature:

6-O-methylerythromycin A N-oxide; With sodium hydrogensulfite; In ethanol; water; at 20 ℃; for 1h;

With sodium carbonate; In ethanol; water;

formaldehyd; With formic acid; sodium carbonate; more than 3 stages;

upstream raw materials:

9-deoxo-9-imino-6-O-methylerythromycin A

clarithromycin 9-oxime

clarythromycin 9-O-(2-pyrimidyl)oxime

6-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-14-ethyl-7,12,13-trihydroxy-4-(5-hydroxy-4-methoxy-4,6-dimethyl-tetrahydro-pyran-2-yloxy)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione 10-(O-pyrimidin-2-yl-oxime)

Downstream raw materials:

4''-O-(((benzyl)amino)-6-oxo-hexyl)carbamoylclarithromycin

4''-O-(((4-fluorobenzyl)amino)-6-oxo-hexyl)carbamoylclarithromycin

4''-O-(((4-methoxybenzyl)amino)-6-oxo-hexyl)carbamoylclarithromycin

4''-O-(((4-hydroxyphenethyl)amino)-6-oxo-hexyl)carbamoylclarithromycin

Refernces

• 1、 Allevi, Pietro,Longo, Alessandra,Anastasia, Mario. "A new convenient transformation of erythromycin a into clarithromycin". . p. 2749 - 2752. Retrieved 1999.
• 2、 -. "A PROCESS FOR PREPARING CLARITHROMYCIN AND CLARITHROMYCIN INTERMEDIATE". Page/Page column 10-13. . Retrieved 2008/06/13.