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

Molecules

Nagendra Prasad Muddala¹  Baskar Nammalwar¹  Subhashini Selvaraju¹  Christina R. Bourne²  Mary Henry³  Richard A. Bunce¹  K. Darrell Berlin¹  Esther W. Barrow³  William W. Barrow³ 

[1] Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA; E-Mails:;Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019, USA; E-Mail:;Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA; E-Mails:

关键词: 2;    4-diaminopyrimidine antifolates;    dihydrofolate reductase (DHFR);    Bacillus anthracis;    pincer complexes;    Heck coupling;   

DOI  :  10.3390/molecules20047222

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.