Templates ligand-based

Recent examples of successful peptide-ligand based discoveries of drug-like peptidomimetics include the discovery of SST antagonists, or the discovery of non-peptidic antagonists of the recently deorphanized urotensin II receptor at Sanofi-Aventis. ° As illustrated in Fig. 3, Flohr etal. used 3D models of the NMR solution structure of cyclic peptide derivatives of Urotensin II as a template for virtual 3D pharmacophore searches which resulted into non-peptidic candidates for lead optimization. 

A monophosphine complex is formed when 3 is mixed with three equivalents of a zinc(ii)salphen complex and half an equivalent of Rh(acac)(CO)2 (acac = acetyl acetonate), whereas the assembly based on template 4 and the zinc(n)salphen complexes forms a bis-phosphine rhodium species. In the latter case, the bisphosphine rhodium complex is completely encapsulated by six salphen building blocks. This difference in mono- versus diphosphine ligation to the Rh -center and, to a lesser extent, the difference in electronic features (and thus donating properties of the phosphine) between template ligands 3 and 4, can be used to induce a different catalytic behavior. 

The ligand-based alignments were carried out using the superposition program FlexS [2], and compound 4j as rigid template (in the conformation obtained by the docking) on the one site and the Multifit routine within the SYBYL software and the same template on the other site (Fig. 11.5). 

Reinhoudt and co-workers (101-105) have reported a series of Schiff base macrocyclic polyether ligand complexes prepared via barium cation-templated Schiff base condensation of the appropriate polyether dialdehyde with a diamine, in the presence of a transition metal or uranyl acetate, followed by removal of the Ba2+ template cation on subsequent addition of guanidinium sulfate (Scheme 19). The copperdl) and nickeldl) complexes (62) and (63) exhibit reversible redox couples... 

The use of absolute similarity and diversity methods provides useful information about overall similarities and differences between molecules, or databases of molecules, but for certain similarity and diversity design applications, the use of a relative measure that is internally referenced to a feature or substructure of interest can provide a more powerful tool. This is true for a receptor-based design and for ligand-based design around a feature or substructure of interest. A common frame of reference enables ligand-based and receptor-based studies to be combined, for example with reagents in an active site and on a template... 

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

Ligand-based Template Design for CPCR-targeted Libraries I 317... 

The Cambridge group has recently developed the chemistry of macrocyclic ligands based upon 2,2 6, 2"-terpyridine 133, 135, 136, 139-143). The macrocycles (Figs. 29 and 30) are prepared by template condensations of... 

K. Varnagy,/. Chem. Soc., Chem. Commun., 1143 (1993). Chiral Quadradentate Ligands Based on Amino Acids Template Syntheses and Properties of the Free Ligands and Their Transition-Metal Complexes. 

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