Compound library preparation

The New Medicines for Trypanosomatidic Infections - NMTrypI project aimed at obtaining new candidate drugs against Trypanosomatidic infections with appropriate efficiency from the lead phase to the final preclinical phase that are more accessible to patients.

Multidisciplinary development of selective anti-parasitic multi-target inhibitors of PTR1/DHFR based on a pteridine scaffold.

Rigid-body docking studies and induced-fit docking studies of pteridine-based compounds to the target proteins TbPTR1, TbDHFR, LmPTR1, LmDHFR and the off-target hDHFR. For both PTR1 variants and human DHFR, conserved structural water sets were considered. Preparations of compound libraries and docking receptors are also covered.

Compound SMILES of resynthesized or newly designed pteridine compounds 1b, 1c, 2a-e, 3a-e, 4a-j and 5a-f used for ligand preparation within Maestro (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Maestro.). SMILES strings and compound identifiers are comma-separated and can be readily imported in Maestro.

Zip archive of N1 protonated reference and newly synthesized pteridines (series 1-5) in SDF format.

Summary of fragments that were used to construct an in silico pteridine library with corresponding fragment identifiers. Connections between the fragments are shown outside the colored boxes. Compounds were composed of a core fragment (C1-C3), an N10 fragment (N1-N7), a PABA fragment (P1-P10) and, for any PABA fragment except P8, P9 and P10, a tail fragment (T1E1-T7).

This SOP describes the preparation of pteridine ligand 3D structures from SMILES or other input formats with the LigPrep routine as embedded in Schrödinger Maestro for usage in docking runs and in silico ADME-Tox property prediction.