N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate monohydrate Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Panobinostat
lactate is a histone deacetylase (HDAC) inhibitor that was approved by the FDA for the treatment of multiple
myeloma. It was also approved for the same indication in
Japan, and the EU approved its use in combination with
bortezomib and dexamethasone for the treatment of adults with
relapsed and/or refractory multiple myeloma. Panobinostat
was discovered and developed by Novartis and is currently
being investigated for a number of hematological cancers as
well as other indications.
Synthese
Grandberg synthesis of 2-methyltryptamine (223) was
accomplished in 47% yield by heating phenylhydrazine (221)
with 5-chloro-2-pentanone (222). Reductive amination of
223 with (E)-3-(4-formyl-phenyl)-acrylic acid methyl ester
(224) and sodium borohydride followed by formation of the
hydrochloride salt provided amine hydrochloride 225 in high
purity. Saponification of the methyl ester followed by reaction
with hydroxylamine provided panobinostat in high overall yield.
The free base was treated with racemic lactic acid and
recrystallized in water to give panobinostat lactate (XXVIII).
N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate monohydrate Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
