title: Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex.
abstract: 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.
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. muddala@okstate.edu.
authors.forename: Nagendra Prasad
authors.initials: NP
authors.lastname: Muddala
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. baskar@okstate.edu.
authors.forename: Baskar
authors.initials: B
authors.lastname: Nammalwar
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. subhas@okstate.edu.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Selvaraju
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019, USA. cbourne@ou.edu.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Bourne
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. henrym@okstate.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Henry
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. rab@okstate.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bunce
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. kdb@okstate.edu.
authors.forename: K Darrell
authors.initials: KD
authors.lastname: Berlin
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. esther.barrow@okstate.edu.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Barrow
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. bill.barrow@okstate.edu.
authors.forename: William W
authors.initials: WW
authors.lastname: Barrow
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001408:Bacillus anthracis / Q000187:drug effects*; D002384:Catalysis; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D010793:Phthalazines; D011743:Pyrimidines; C017205:2,4-diaminopyrimidine; D010165:Palladium