Important Targets

SCHEME 9.19 Invoked mechanism for one-pot oxidative multicomponent BigineUi reaction. 

SCHEME 9.20 SnCl -catalyzed BigineUi reaction using P-oxodithioesters as dicarbonyl compound. 

The compatibility of this methodology with a variety of different substitnted reactants and the stability shown by them under these acidic conditions, together with the recyclability of the catalyst without losing catalytic activity, make this strategy highly nseful. 

Many efforts have been invested in the discovery of new active dihydropyrrmidones (DHPMs), which have been found to possess a wide range of biological activity (Fig. 9.5) [6]. Although racemic DHPMs are easy accessible 

SCHEME 9.21 Mechanistic hypothesis for the synthesis of 5-methylmercaptothiocarbonyM-aryI-3,4-dihydropyriinidin-2(IW)-ones 53 and substituted 2f/-chromen-2-thiones 55. 

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Littie work has been reported on the biodegradation of dimethyUiydrazine, but it may become an important target for remediation at some sites... 

The substrate specificity of ACE is low. ACE cleaves a variety of pairs of amino acids from the carboxy-terminal part of several peptide substrates. The conversion of ANGI to ANGII and the degradation of bradykinin to inactive fragments are considered the most important functions of ACE. Both peptides have profound impact on the cardiovascular system and beyond. ACE is thus an important target for ACE inhibitors. These compounds are frequently and efficiently used in the treatment of hypertension and cardiac failure. 

Finally, drug treatment in the elderly is of great importance and warrants special attention with regard to safety and tolerability, since systolic blood pressure is recognized as an important target for treatment, particularly in older persons. The benefits of antihypertensive treatment in the elderly and in patients with isolated systolic hypertension are greater than in younger persons. 

Also nonkinase molecules might be important targets for anticancer drugs. For instance, the activity of the mitotic kinesin Eg5 (KSP, kinesin-5) can be inhibited by small molecules (e.g., monastrol, KSP-IA) resulting in mitotic defects associated with the induction of apoptosis. 

Szapary PO, Rader DJ (2004) The triglyceride-high-density lipoprotein axis an important target of therapy Am Heart J 148 211-221... 

NCEP ATP III identified metabolic syndrome as an important target for further reducing CHD risk. Treatment of metabolic syndrome starts with increased physical activity, weight reduction (which also enhances LDL cholesterol lowering and... 

Puzas JE, Sickel MJ, Felter ME. 1992. Osteoblasts and chondrocytes are important target cells for the toxic effects of lead. Neurotoxicology 13(4) 783-788. 

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