93871-78-4Relevant articles and documents
Identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign
Bandiera, Tiziano,Bartoccini, Francesca,Bertozzi, Fabio,Bertozzi, Sine Mandrup,Bolognesi, Maria Laura,Borsari, Chiara,Brambilla, Enzo,Cavalli, Andrea,Conti, Paola,Cordeiro da Silva, Anabela,Costi, Maria Paola,Cullia, Gregorio,Ellinger, Bernhard,Ferrari, Stefania,Goldoni, Luca,Gul, Sheraz,Kuzikov, Maria,Linciano, Pasquale,Piersanti, Giovanni,Pinto, Andrea,Piomelli, Daniele,Prati, Federica,Retini, Michele,Rizzo, Vincenzo,Roberti, Marinella,Santucci, Matteo,Witt, Gesa,Santarém, Nuno
, (2020/01/29)
The LIBRA compound library is a collection of 522 non-commercial molecules contributed by various Italian academic laboratories. These compounds have been designed and synthesized during different medicinal chemistry programs and are hosted by the Italian Institute of Technology. We report the screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase 1, TbPTR1 and LmPTR1. Nine compounds were active against parasitic PTR1 and were selected for cell-based parasite screening, as single agents and in combination with methotrexate (MTX). The most interesting TbPTR1 inhibitor identified was 4-(benzyloxy)pyrimidine-2,6-diamine (LIB_66). Subsequently, six new LIB_66 derivatives were synthesized to explore its Structure-Activity-Relationship (SAR) and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The results indicate that PTR1 has a preference to bind inhibitors, which resemble its biopterin/folic acid substrates, such as the 2,4-diaminopyrimidine derivatives.
Synthesis of Some Substituted Guanidinopyrimidines and their Structural Assignment by 13C and 1H NMR
Ladd, David L.
, p. 917 - 921 (2007/10/02)
A series of substituted 2- and 4-guanidinopyrimidines were prepared by reaction of halopyrimidines with guanidine; alkylamino and amino substituents were introduced by subsequent halogen replacement by primary amines or ammonia or the catalytic reduction of nitro groups.Structural assignments were made on the basis of 13C and 1H nmr.A guanidinopteridine and a bispyrimidinylguanidine were also synthesized.Some unsuccessful reaction illustrated the low nucleophilic reactivity and thermal instability of the guanidine group.
