Scaffold compounds

The most X-ray intensive screening method was described by Card et al. [8] on the design of phosphodiesterase (PDE) inhibitors (Figure 1.7). The authors initially biochemically screened a 20,000 member library of small molecular weight (120-350 MW) core scaffold compounds against 5-PDE isoforms at 200 pM. Multiple isoforms of PDE were used in order to eliminate the number of false positives obtained from the screen. There were 316... 

PDE4 (Table 1, entry 10) A library of about 20,000 "scaffold" compounds with molecular weights of 125-350 Da were screened in a combination of biochemical assays and crystallography studies to identify the PDE4 inhibitor pyrazole ester derivative 38 [45]. A 4000-fold increase in potency was achieved after only two rounds of chemical synthesis to give 39. 

Fig. 5 Shape-persistent Hekates based on oligo(phenyleneethynylene) scaffolds. Compounds 14 and 15 form columnar mesophases. For stars 16 (R = H or fullerene, R = C10H2i) thermotropic properties have not been published...

Fig. 3.8 Despite their common scaffold, compound 33 is a selective fibrinogen (GPIIb/llla) receptor ligand, whereas 34 is a selective vitronectin (a,fl3) receptor ligand their selectiv-ities differ by more than seven orders of magnitude.

Because all of the azidocoumarin scaffold compounds show no or very weak fluorescence and most of the reactions would proceed quantitatively, they directly... 

The 2-azadiene system of the pyrazinone scaffold undergoes inter- and intramolecular cycloaddition reactions with a variety of (functionalized) alkenes forming bicyclic adducts, leading to the stereoselective generation of a variety of natural product analogues as well as peptidomimetics [58]. These bicyclic compounds could serve as key intermediates in the synthesis... 

The 2(lH)-pyrazinone system has received increased interest in the past two decades by both synthetic and biological research, due to its presence in a variety of natural and non-natural products as well as pharmacologically active compounds. The easy and diverse methods for the generation of this versatile scaffold make it a prime choice for the current pharmaceutical research hke thrombin inhibitors, substance P antagonists, etc. The rich 1,4-azadiene... 

The condensation between enaminones and cyanoacetamide is a well-established method for the synthesis of 2-pyridones (see c, Scheme 2, Sect. 2.1), and the use of malonodinitrile instead of the amide component has also been shown to yield 2-pyridones [39-41]. Recently, Gorobets et al. developed a microwave-assisted modification of this reaction suitable for combinatorial synthesis, as they set out to synthesize a small library of compounds containing a 2-pyridone scaffold substituted at the 3, 5, and 6-positions [42]. The 2-pyridones were prepared by a three-component, two-step reaction where eight different carbonyl building blocks were reacted with N,N-dimethylformamide dimethyl acetal (DMFDMA) to yield enaminones 7 (Fig. 2). The reactions were performed under solvent-free conditions at el-... 

Fig. 3. Known and hitherto elusive perethynylated building blocks for two- and three-dimensional acetylenic scaffolding. The only compounds shown are those with either free or silyl-protected ethynyl groups...

In contrast, the synthesis of tetraethynylethene (TEE, C10H4) was described in 1991 and, since then, a rich variety of cyclic and acyclic molecular scaffolds incorporating this carbon-rich molecule as a construction module have been prepared. The majority of these compounds, such as the expanded radialenes or the oligomers and polymers of the poly(triacetylene) type, are highly stable and... 

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