Evaluation of New Dihydrophthalazine-Appended  2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex

Nagendra Prasad Muddala; Baskar Nammalwar; Subhashini Selvaraju; Christina R. Bourne; Mary Henry; Richard A. Bunce; K. Darrell Berlin; Esther W. Barrow; William W. Barrow

doi:10.3390/molecules20047222

Molecules (Apr 2015)

Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex

Nagendra Prasad Muddala,
Baskar Nammalwar,
Subhashini Selvaraju,
Christina R. Bourne,
Mary Henry,
Richard A. Bunce,
K. Darrell Berlin,
Esther W. Barrow,
William W. Barrow

Affiliations

Nagendra Prasad Muddala: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Baskar Nammalwar: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Subhashini Selvaraju: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Christina R. Bourne: Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019, USA
Mary Henry: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
Richard A. Bunce: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
K. Darrell Berlin: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Esther W. Barrow: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
William W. Barrow: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA

DOI: https://doi.org/10.3390/molecules20047222
Journal volume & issue: Vol. 20, no. 4
pp. 7222 – 7244

Abstract

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The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140 °C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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