Affinity-enhancing 5,7-hydrophobic substituents

Haloallyl amines also have been studied as inhibitors of SSAO. The 2-aryl-3-haloallylamines proved to be potent irreversible inhibitors of rat aorta SSAO. Hydrophobic substituents on the aryl ring enhanced activity, while phenolic groups decreased activity [78]. The MAO B selective ( )-2-(3, 4 -dimethoxyphe-nyl)-3-fluoroallylamine (22d) inhibited rat SSAO in vascular and brown adipose tissues and was selective relative to inhibition of MAO A [79]. MDL 72974A (25) is a potent irreversible inhibitor of both MAO B and SSAO with a 190-fold lower affinity for MAO A [80]. 

Small hydrophobic substituents enhance the binding affinity at positions 4,12(3, 14, and 16a. 

Hydrophobic interactions exerted by substituents at position 5 of cytosine or uracil enhance stability of DNA/RNA-hybrids (70,71) [163]. Derivatives with longer alkyl chains reduce duplex stability [169], with aminoalkyl residues being an exemption [170]. Above all, ethinyl substitution at position C5 of pyrimidine bases results in significantly increased binding affinity, as shown with binding of modified poly(rU) and poly(rA) [164]. Also, substitution with propinyl showed the same effect (73,74), which was attributed to ji-ji-interactions of the alkinyl substituent with the nucleobase in the 5 -neighbourhood. Oligomers of this type form duplexes with RNA, which can activate RNase-H. Since there is only a minor influence on nuclease resistance, such modifications are preferentially applied in combination... 

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