GPCR-Targeted Libraries

S. A., Okun, L, Ivashchenko, A.A., and Savchuk, N.P. Property-based design of GPCR-targeted library./. Chem. Inf. Comput. Sci. 2002, 42, 1332-1342. 

Mason and coworkers reported one of the first examples of a target class library design utilizing 3D pharmacophore descriptors (20). In this example, the authors designed a set of GPCR-targeted libraries based on Ugi chemistry... 

For example, one might design a GPCR target class library in which the coverage of GPCR-relevant 3D pharmacophores is maximized, while the coverage of PGP substrate pharmacophores is minimized in the selected products. 

Ligand-based Template Design for GPCR-targeted Libraries I 315... 

Figure 9 Two examples of GPCR target class libraries prepared by solid-phase synthesis reported by industrial groups. In both cases, an example of a neurokinin I receptor ligand discovered is shown...

Spiropiperidines have the ability to orient substituents in mimicry of a peptidic [3-tum which could explain their activity against a range of peptidic GPCR targets. Ono Pharmaceuticals developed a solid phase combinatorial library based upon the Ugi reaction to generate potential lead matter for a range of chemokine receptors. From their initial 576-compound collection, several compounds showed low... 

The subset screen of lactate bioisosteres and GPCR target class chemical libraries identified the singleton compound 8. The compound had a reproducible top effect of 70% and an EC50 of 1.6 pM. No activity against the nicotinic acid receptor (hu GPR109a) was detected (Scheme 21.5). 

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