235114-32-6

Basic information

• Product Name: Micafungin
• Synonyms: MICAFUNGIN;Micafungin (Acid);PneuMocandin A0,1-[(4R,5R)-4,5-dihydroxy-N2-[4-[5-[4-(pentyloxy)phenyl]-3-isoxazolyl]benzoyl]-L-ornithine]-4-[(4S)-4-hydroxy-4-[4-hydroxy-3-(sulfooxy)phenyl]-L-threonine]-;Micafungin-d11
• CAS NO: 235114-32-6
• Molecular Formula: C56H71N9O23S
• Molecular Weight: 1270.28
• EINECS: 1806241-263-5
• Product Categories: Antifungals;Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;API
• Mol File: 235114-32-6.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Density: 1.62 g/cm³
• Refractive Index: 1.706
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Very Slightly, Heated)
• PKA: -4.46±0.18(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: Micafungin(CAS DataBase Reference)
• NIST Chemistry Reference: Micafungin(235114-32-6)
• EPA Substance Registry System: Micafungin(235114-32-6)

Safety Data

• Hazardous Substances Data: 235114-32-6(Hazardous Substances Data)

Usage

Description

Micafungin, also known as Mycamine or Funguard, is a semi-synthetic cyclic lipopeptide echinocandin antifungal drug. It is derived from FR901379, which is obtained by enzymatic cleavage of the naturally occurring echinocandin FR-901379, derived from the fungus Coleophoma empedri. Micafungin works by inhibiting the synthesis of 1,3-beta-D-glucan, an essential polysaccharide of the cell wall of many pathogenic fungi, and is used in its sodium salt form for the treatment of invasive candidiasis and aspergillosis in patients who are intolerant of other therapy.

Uses

Used in Antifungal Treatments:
Micafungin is used as an antifungal agent for the treatment of various fungal infections caused by Aspergillus and Candida spp., such as fungaemia, respiratory and gastrointestinal mycoses. It has a marked fungicidal effect on almost all species of Candida, including fluconazole-resistant strains, and a fungistatic effect on a range of Aspergillus species.
Used in Combination Therapy:
Micafungin is used in combination with other drugs, such as the HIV protease inhibitor ritonavir, as well as transplant medications like cyclosporine and tacrolimus, to enhance treatment efficacy and address drug resistance issues.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Micafungin is used as an active pharmaceutical ingredient in the development of antifungal medications, specifically for the treatment of invasive candidiasis and aspergillosis. Its unique mechanism of action and effectiveness against resistant strains make it a valuable asset in the fight against fungal infections.

References

https://www.drugbank.ca/drugs/DB01141 https://en.wikipedia.org/wiki/Micafungin

Originator

Fujisawa (Japan)

Antimicrobial activity

It is active against Aspergillus spp., Candida spp. and the cyst form of Pn. jirovecii. Resistance has rarely been reported.

Pharmaceutical Applications

A semisynthetic lipopeptide derived from a fermentation product of Coleophoma empetri. Formulated as the monosodium salt for intravenous infusion.

Pharmacokinetics

Cmax 50 mg 1-h infusion: c. 5 mg/L 1 h post infusion Plasma half-life: 11–15 h Volume of distribution: 0.4 L/kg Plasma protein binding: 99% Blood concentrations increase in proportion to dosage. Unlike anidulafungin and caspofungin, a loading dose is not required. Distribution The drug is widely distributed, the highest concentrations being found in the liver. Levels in the CSF and urine are negligible. Metabolism and excretion It is metabolized by the liver and the three inactive metabolites are excreted in the feces (70%). Less than 1% of a dose is eliminated as unchanged drug in the urine. No dosage adjustment is required in patients with severe renal impairment or mild to moderate hepatic impairment. The effect of severe hepatic impairment on micafungin pharmacokinetics has not been studied. Micafungin is not cleared by hemodialysis.

Clinical Use

Candidemia and certain invasive forms of candidosis Esophageal candidosis Prophylaxis of Candida infections in hematopoietic stem cell transplant (HSCT) recipients

Side effects

Occasional histamine-mediated infusion-related reactions, injection site reactions and transient abnormalities of liver enzymes have been reported. Isolated cases of significant hepatic or renal dysfunction, hepatitis, or liver or renal failure have also been described.

Drug interactions

Potentially hazardous interactions with other drugs Ciclosporin: possibly increases ciclosporin concentration. Sirolimus: increases sirolimus concentration.

Metabolism

Metabolised in the liver by arylsulfatase to its catechol form and further metabolised to the methoxy form by catechol-O-methyltransferase. Some hydroxylation to micafungin via cytochrome P450 isoenzymes also occurs. Exposure to these metabolites is low and metabolites do not contribute to the overall efficacy of micafungin. After 28 days about 71% of a dose is recovered in the faeces and 12% in the urine.

InChI:InChI=1/C56H71N9O23S/c1-4-5-6-17-86-32-14-11-28(12-15-32)39-21-33(63-87-39)27-7-9-29(10-8-27)49(75)58-34-20-38(70)52(78)62-54(80)45-46(72)25(2)23-65(45)56(82)43(37(69)22-41(57)71)60-53(79)44(48(74)47(73)30-13-16-36(68)40(18-30)88-89(83,84)85)61-51(77)35-19-31(67)24-64(35)55(81)42(26(3)66)59-50(34)76/h7-16,18,21,25-26,31,34-35,37-38,42-48,52,66-70,72-74,78H,4-6,17,19-20,22-24H2,1-3H3,(H2,57,71)(H,58,75)(H,59,76)(H,60,79)(H,61,77)(H,62,80)(H,83,84,85)/t25-,26-,31+,34-,35-,37+,38+,42-,43-,44-,45-,46-,47-,48-,52+/m0/s1

Upstream product

• 168110-44-9 FR 179642 
• 3140-73-6 2-chloro-4,6-dimethoxy-1 ,3,5-triazine 
• 179162-55-1 4-{5-[4-(pentyloxy)phenyl]-1,2-oxazol-3-yl}benzoic acid 
• 2592-95-2 benzotriazol-1-ol 
• 1426839-86-2 C₂₇H₂₈N₃O₉P 
• 1426839-89-5 C₂₁H₂₀ClNO₃ 
• 235112-66-0 1-[[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]oxy]-1H-1,2,3-benzotriazole 

Relevant articles and documents

INTERMEDIATES AND PROCESSES TO PREPARE MICAFUNGIN

The present invention relates to active esters of compound of Formula I-A and Formula I-B which are used as key intermediates in the synthesis of Micafungin, an antifungal agent and process of preparation of said active esters. The invention also relates to process of preparing Micafungin from said active esters.

PREPARATION OF MICAFUNGIN INTERMEDIATES

The present invention relates to the preparation of compounds, in particular to the preparation of compounds of formula (I), which may be used with a compound of formula (VI), or a salt thereof as intermediates for the preparation of antifungal agents, preferably micafungin (MICA) or a salt thereof.

Novel echinocandin antifungals. Part 2: Optimization of the side chain of the natural product FR901379. Discovery of micafungin

Further optimization of the potent antifungal activity of side chain analogs of the natural product FR901379 led to the discovery of compound 8 with an excellent, well-balanced profile. Potent compounds with reduced hemolytic potential were designed based upon a disruption of the linearity of the terphenyl lipophilic side chain. The optimized compound (8, FK463, micafungin) displayed the best balance and was selected as the clinical candidate.