80615-53-8Relevant articles and documents
Chemical Space Exploration around Thieno[3,2- d]pyrimidin-4(3 H)-one Scaffold Led to a Novel Class of Highly Active Clostridium difficile Inhibitors
Shao, Xuwei,Abdelkhalek, Ahmed,Abutaleb, Nader S.,Velagapudi, Uday Kiran,Yoganathan, Sabesan,Seleem, Mohamed N.,Talele, Tanaji T.
, p. 9772 - 9791 (2019/11/03)
Clostridium difficile infection (CDI) is the leading cause of healthcare-associated infection in the United States. Therefore, development of novel treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 μM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one) with improved potency (MIC = 19/38 μM), selectivity over normal gut microflora, CC50s > 606 μM against mammalian cell lines, and acceptable stability in simulated gastric and intestinal fluid. Further optimization of 6a at C2-, N3-, C4-, and C7-positions resulted in a library of >50 compounds with MICs ranging from 3 to 800 μM against clinical isolates of C. difficile. Compound 8f (MIC = 3/6 μM) was identified as a promising lead for further optimization.
Distamycin-NA: A DNA Analog with an Aromatic Heterocyclic Polyamide Backbone: Part 1 - Synthesis and Structural Analysis of Monomers and Dimers Containing the Nucleobase Uracil
Sauter, Guido,Stulz, Eugen,Leumann, Christian
, p. 14 - 34 (2007/10/03)
The synthesis of the monomeric building block 13 and its constitutional isomer 12 of a new type of DNA analog, distamycin-NA, is presented (Schemes 1 and 2). This building block consists of a uracil base attached to a thiophene core unit via a biaryl-like axis. Next to the biaryl-like axis on the thiophene chromophore, a carboxy and an amino substituent are located allowing for oligomerization via peptide coupling. The proof of constitution and the conformationsl preferences about the biaryl-like axis were established by means of X-ray analyses of the corresponding nitro derivatives 10 and 11. Thus, the uracil bases are propeller-twisted relative to the thiophene core, and bidentate H-bonds occur between two uracil bases in the crystals. The two amino-acid building blocks 12 and 13 were coupled to give the dimers 15 and 16 using dicyclohexylcarbodiimide (DCC) in THF/LiCl and DMF, respectively. While the dimer 15 showed no atropisomerism on the NMR time scale at room temperature, its isomer 16 occurred as distinct diastereoisomers due to the hindered rotation around its biaryl-like axis. Variable-temperature 1H-NMR experiments allowed to determine a rotational barrier of 19 ± 1 kcal/mol in 16. The experimental data were complemented by AM1 calculations.
THE PREPARATION OF 2-(HETEROCYCLIC)THIENOPYRIDINE DERIVATIVES
Elliot, Richard, L.,O'Hanlon, Peter J.,Rogers, Norman H.
, p. 3295 - 3302 (2007/10/02)
The preparation of a series of 2-(heterocyclic)-4-ethyl-4,7-dihydro-7-oxothienopyridine-6-carboxylic acids (5j-l) by aminolysis of the corresponding 2-bromo derivative (5i) is described.None of the compounds (5j-l) showed any interesting antibacterial activity.
