66 research outputs found
Structure–activity relationships of a novel pyranopyridine series of Gram-negative bacterial efflux pump inhibitors
Recently we described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-negative efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-β-naphthylamide (PAβN), D13-9001, and the pyridopyrimidine derivatives. Here, we report the synthesis and biological evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a molecular activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility. Several compounds, such as 22d–f, 22i and 22k, are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli
ChemInform Abstract: Synthesis of Novel Condensed Pyridines and Pyrido[2,3-d]pyrimidines.
Synthesis and Anticonvulsant Activity of Derivatives of Pyrano[4′,3′:4,5]pyrido[2,3-b]furo[3,2-d]pyrimidine and Pyrano[4′,3′:4,5]pyrido[2,3-b]furo[3,2-d]pyridine.
ChemInform Abstract: Synthesis and Antiarrythmical Activity of 7-Benzyl- and 7-Ethyl-1- hydroxy-4-carbamoyl-3-oxo-5,6-dihydro-8H-2,7-naphthyridine.
ChemInform Abstract: Synthesis of Condensed 3-Cyanopyridin-2(1H)-ones Based on the Smiles Rearrangement.
ChemInform Abstract: Synthesis and Neurotropic Properties of 1-Amino-2-substituted-8,9-dihydro-6H-pyrano(thiopyrano)[4,3-d]thieno [2,3-b]pyridines and -thieno[2,3-c][2,7]naphthyridines.
ChemInform Abstract: Synthesis and Biological Activities of Pyrano(4,3-d)furo(2,3-b) pyridine Derivatives
ChemInform Abstract: Synthesis and Antispasmodic Activity of Derivatives of Pyrazolo[3,4-b]pyrano(thiopyrano)[4,3-d]pyridines and Pyrazolo[3,4-c]isoquinolines.
ChemInform Abstract: Synthesis of 2,4-Disubstituted Pyrimido(4,5-b)indoles, Pyrano(4′,3′:4, 5)pyrrolo(2,3-d)pyrimidines and Some Conversions of Pyrimido(4,5-b) indoles.
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