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====Anti-angiogenesis====
Angiogenesis or the growth of new blood vessels has been reported to correspond with MM progression where [[vascular endothelial growth factor]] (VEGF) and its receptor, [[bFGF]]<ref name=Bartlett2004 />
====Anti-tumor activity====
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On the phenyl ring, a 3,4-dialkoxyphenyl moiety (Figure 6) is a known pharmacophore in PDE4 inhibitors such as [[rolipram]]. Optimal activity is achieved with a methoxy group at the 4-position (X2) and a bigger group, such as cyclopentoxy at the 3-position carbon (X3). However the thalidomide PDE4 inhibitory analogs do not follow the SAR of rolipram analogs directly. For thalidomide analogs, an ethoxy group at X3 and a methoxy group at X2, with X1 being just a hydrogen, gave the highest PDE4 and TNF-α inhibition.<ref name=Man2009 /> Substitutes larger than diethoxy at the X2–X3 position had decreased activity. The effects of these substitutions seem to be mediated by steric effects.<ref name=Muller1996 />
For the Y-position, a number of groups have been explored. Substituted amides that were larger than [[methylamide]] (CONHCH<sub>3</sub>) decrease PDE4 inhibition activity.<ref name=Muller1996 /> Using a carboxylic acid as a starting point, an amide group has similar PDE4 inhibition activity but both groups were shown to be a considerably less potent than a methyl ester group, which had about six-fold increase in PDE4 inhibitory activity. Sulfone group had similar PDE4 inhibition as the methyl ester group. The best PDE4 inhibition was observed when a nitrile group was attached, which has 32 times more PDE4 inhibitory activity than the carboxyl acid.<ref name=Man2009 /> Substituents at Y leading to increasing PDE4 inhibitory activity thus followed the order:
: COOH ≤ CONH<sub>2</sub> ≤ COOCH<sub>3</sub> ≤ SO<sub>2</sub>CH<sub>3</sub> < CN
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