89567-06-6Relevant articles and documents
Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni
De Schutter, Joris W.,Morrison, James P.,Morrison, Michael J.,Ciulli, Alessio,Imperiali, Barbara
, p. 2099 - 2118 (2017/03/17)
The glycoproteins of selected microbial pathogens often include highly modified carbohydrates such as 2,4-diacetamidobacillosamine (diNAcBac). These glycoconjugates are involved in host-cell interactions and may be associated with the virulence of medically significant Gram-negative bacteria. In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. We performed fragment-based and high-throughput screens against an amino-sugar acetyltransferase enzyme, PglD, involved in biosynthesis of UDP-diNAcBac in Campylobacter jejuni. Herein we report optimization of the hits into potent small molecule inhibitors (IC50 300 nM). Biophysical characterization shows that the best inhibitors are competitive with acetyl coenzyme A and an X-ray cocrystal structure reveals that binding is biased toward occupation of the adenine subpocket of the AcCoA binding site by an aromatic ring.
A novel microwave-assisted green synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones under solvent-free conditions
Jain, Kishor S.,Bariwal, Jitender B.,Phoujdar, Manisha S.,Nagras, Madhuri A.,Amrutkar, Rakesh D.,Munde, Manoj K.,Tamboli, Riyaj S.,Khedkar, Samrat A.,Khiste, Rahul H.,Vidyasagar, Nikhil C.,Dabholkar, Vinit V.,Kathiravan
body text, p. 178 - 185 (2009/07/19)
A rapid microwave-assisted green chemical synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones 3, 4, and 5 involving the condensation of a variety of nitriles with o-aminoesters of thiophene 2a-e, benzene 2f, dimethoxybenzene 2g and quinazolinone 2h in the presence of catalytic amount of HCl alone or with the Lewis acid AlCl3 under solvent-free conditions, is described for the first time. This novel and clean one-pot methodology, which is characterized by very short reaction times and easy workup procedures, can be exploited to generate a diverse library of condensed pyrimidine heterocycles.
Synthesis and antihyperlipidemic activity of some novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-disubstituted pyrimidines
Kathiravan, Matthu K.,Shishoo, Chamanlal J.,Kumar, Krishnan Girish,Roy, Saroj Kumar,Mahadik, Kakasheb R.,Kadam, Shivajirao S.,Jain, Kishor S.
, p. 599 - 606 (2008/03/13)
Synthesis and antihyperlipidemic activity of a series of novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-di-substituted pyrimidines are described. The design of these compounds is based on the earlier QSAR study on the antihyperlipidemic 2-substituted
Synthesis and pharmacological study of antihyperlipaemic activity of 2-substituted thieno(2,3-d)pyrimidin-4(3H)-ones
Shishoo,Devani,Bhadti,Jain,Rathod,Goyal,Gandhi,Patel,Naik
, p. 567 - 572 (2007/10/02)
A series of 2-substituted thieno(2,3-d)pyrimidin-4-(3H)-ones (1-15) was prepared by the reaction of thiophene ortho-aminoester (IV) with a variety of nitriles (V) under acidic conditions, and screened for antihyperlipaemic activity in various and animals
