Neuropeptide S Library Chem Div Inc 2017 Knowledge

Neuropeptide S Library Chem. Div Inc. 2017

Knowledge Progression & Selection Reference Compounds ► 2 D Similarity ► 3 D Pharmacophore modeling ► Expert opinion Thomson Integrity Neuropeptide S Library ~3 k cmpds Ch. EMBL Sci. Finder ► Scaffold prioritization ► Med. Chem Filters ► scaffold hopping ► 2 D topological & 3 D similarity

Reference compounds.

Methodology for compound selection Ø All chemotypes presented in the reference library have been investigated for the common motives. The fragments, crucial for high potency have been predicted on the basement of literature review* and expert opinion. (Among this moieties are hydrophobic or aromatic fragments and HBA) Ø Several 3 D ligand-based pharmacophore hypothesis have been created in Schrödinger Maestro. The examples are presented on the picture below. Examples of reference compounds in violet. Reference compound Chem. Div E 786 -2035 Reference compound Chem. Div E 019 -0609 * Ruzza C. , Calò G. , Di Maro S. et. al. Neuropeptide S receptor ligands: a patent review (2005 -2016). Expert Opin Ther Pat. 2017 Mar; 27(3): 347 -362.

Descriptor Distributions 5 Diversity 0. 8 Clusters (Tanimoto, min cmpds per cluster – 5, similarity threshold 0. 5) 184 Diversity in heterocycles 0. 9 Singletones 753 Avr structures in clusters 14. 2

Library statistics. Scaffold examples 6

Representative compounds from the library 7

Thank you