Description
Anecortave acetate, an angiogenesis inhibitor, was launched
in Australia by Alcon for the treatment of age-related
macular degeneration (AMD). AMD is the leading cause of
untreatable blindness among people aged 65 to 74 years in
the U.S. Worldwide, approximately 20 to 25 million people suffer from AMD, a disease that until recently was untreatable.
Anecortave, an angiostatic steroid, down-regulates the
expression MMP-2 and -9 to exert its antiangiogenic effects.
Chemical Properties
Off-White Solid
Uses
As an angiostatic steroid, Anecortave Acetate can be used in treatment of macular degeneration.
Definition
ChEBI: Anecortave acetate is an organic molecular entity.
Synthesis
Anecortave has been synthesized by several different
routes, and Pharmacia process patents are cited here.
The synthesis is depicted in the scheme. Compound 1 was
condensed with 2-chlorovinyl ethyl ether with n-BuLi in
THF at low temperature to give a mixture of two isomeric
aldehydes 2 in 91% yield. The mixture 2 was treated with
acetic anhydride and anhydrous potassium acetate in DMF at
106C to give acetate 3 which was reacted with RhCl(PPh3)3
and triethylsilane in methylene chloride at 45C for 4 hours
to yield the corresponding triethylsilane ether 4 as a solid
after crystallization in hexane. Finally, compound 4 was oxidized
with 40% peracetic acid in toluene at low temperature,
and the reaction was quenched with SO2 in methanol (2M),
and treated with TEA to give anecortave acetate
.
Enzyme inhibitor
This novel angiogenesis pro-drug (FW = 386.48 g/mol; CAS 7753-60-8) is taken up and metabolically de-esterified to form the aqnecortave, a synthetic steroid that suppresses the development and elongation of neovascular sprouts and tip cell motility in a VEGF-treated retinal explant model in a dose-dependent manner. Whether used as monotherapy or in combination with sub-therapeutic doses of cisplatin, anecortave acetate significantly controlled tumor burden in a murine retinoblastoma model.
