micafungin sodium

• C56-H70-N9-O23-S.Na
  1292.265
  Fujisawa (Originator), Merck & Co. (Codevelopment)
  Antifungal Agents, ANTIINFECTIVE THERAPY, 1,3-beta-Glucan Synthase Inhibitors, Echinocandins
  Launched-2002

{5-[(1S,2S)-2-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-3-[(1R)-2-carbamoyl-1-hydroxyethyl]-11,20,21,25-tetrahydroxy-15-[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-18-[(4-{5-[4-(pentyloxy)phenyl]-1,2-oxazol-3-yl}benzene)amido]-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^9,13]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid

June 24, 2013 , Astellas Pharma US, Inc. (“Astellas”), a U.S. subsidiary of Tokyo-based Astellas Pharma Inc. (Tokyo: 4503), announced that the U.S. Food and Drug Administration (FDA) has approved its Supplemental New Drug Application (sNDA) for the use of MYCAMINE® (micafungin sodium) for injection by intravenous infusion for the treatment of pediatric patients four months and older with candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplants (HSCT).

http://www.drugs.com/newdrugs/fda-approves-pediatric-indication-astellas-mycamine-micafungin-sodium-3827.html

Micafungin (trade name Mycamine) is an echinocandin antifungal drug developed by Astellas Pharma. It inhibits the production of beta-1,3-glucan, an essential component of fungal cell walls. Micafungin is administered intravenously. It received final approval from the U.S. Food and Drug Administration on March 16, 2005, and gained approval in the European Union on April 25, 2008.

Micafungin is indicated for the treatment of candidemia, acute disseminated candidiasis, Candida peritonitis, abscesses and esophageal candidiasis. Since January 23, 2008, micafungin has been approved for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation (HSCT).

Micafungin works by way of concentration-dependent inhibition of 1,3-beta-D-glucan synthase resulting in reduced formation of 1,3-beta-D-glucan, which is an essential polysaccharide comprising one-third of the majority of Candida spp. cell walls. This decreased glucan production leads to osmotic instability and thus cellular lysis

• Micafungin sodium, FK-463, Mycamine, Funguard,208538-73-2

• The synthesis of FK-463 can be performed as follows: The enzymatic deacylation of FR-901379 with Streptomyces anulatas No. 4811, S. anulatas No. 8703, Streptomyces strain No. 6907 or A. utahensis IFO13244 gives the deacylated lipopeptide FR-179642 (1), which is then reacylated with 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]benzotriazole 3-oxide (VI) by means of dimethylaminopyridine (DMAP) in DMF. The acylating compound (VI) can be obtained as follows: The cyclization of 4-pentyloxyphenylacetylene (I) with 4-(hydroxyiminomethyl)benzoic acid methyl ester (II) by means of triethylamine in hot THF gives 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid methyl ester (III), which is hydrolyzed with NaOH in hot THF/water yielding the corresponding free acid (IV). Finally, this compound is condensed with 1-hydroxybenzotriazole (V) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDMCA) in dichloromethane.
  Fromtling, R.A.; Castr, Drugs Fut 1998, 23, 12, 1273
  The synthesis of FK-463 can be performed as follows: The enzymatic deacylation of FR-901379 with Streptomyces anulatas No. 4811, S. anulatas No. 8703, Streptomyces strain No. 6907 or A. utahensis IFO13244 gives the deacylated lipopeptide FR-179642 (1), which is then reacylated with 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]benzotriazole 3-oxide (VI) by means of dimethylaminopyridine (DMAP) in DMF. The acylating compound (VI) can be obtained as follows: The cyclization of 4-pentyloxyphenylacetylene (I) with 4-(hydroxyiminomethyl)benzoic acid methyl ester (II) by means of triethylamine in hot THF gives 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid methyl ester (III), which is hydrolyzed with NaOH in hot THF/water yielding the corresponding free acid (IV). Finally, this compound is condensed with 1-hydroxybenzotriazole (V) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDMCD) in dichloromethane.

• 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego)1998,:Abst F-145