4464-60-2Relevant articles and documents
Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure-Activity Relationship, Metabolism, and Biology Triaging
Van Der Westhuyzen, Renier,Mabhula, Amanda,Njaria, Paul M.,Müller, Rudolf,Ngumbu Muhunga, Denis,Taylor, Dale,Lawrence, Nina,Njoroge, Mathew,Brunschwig, Christel,Moosa, Atica,Singh, Vinayak,Rao, Srinivasa P.S.,Manjunatha, Ujjini H.,Smith, Paul W.,Warner, Digby F.,Street, Leslie J.,Chibale, Kelly
supporting information, p. 9444 - 9457 (2021/07/19)
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
Synthesis of heteroarenecarbonitriles by electrophilic cyanation; Reaction of metalated heteroarenes with p-toluenesulfonyl cyanide
Nagasaki, Izuru,Suzuki, Yumiko,Iwamoto, Ken-Ichi,Higashino, Takeo,Miyashita, Akira
, p. 443 - 450 (2007/10/03)
Several heteroarenecarbonitriles (5) were synthesized in moderate yields from heteroarenes (3) through metalation, followed by electrophilic cyanation using p-toluenesulfonyl cyanide. Similarly, trimethylsilylheteroarenes (8) were converted to heteroarenecarbonitriles (5) in good yields by treatment with p-toluenesulfonyl cyanide.
Diheteroarylmethanes. IV. Oxidations and Metal-promoted Coupling Reactions of Bis(benzoheteroaryl)methanes
Bradamante, Silvia,Facchetti, Antonio,Pagani, Giorgio A.
, p. 329 - 338 (2007/10/03)
Bis(2-benzothiazolyl)methane, 1, bis(benzoxazolyl)methane, 2, and bis(N-methyl-2-benzimidazolyl)methane, 3, undergo easy oxidation by common oxidizing agents (air, KMnO4, K2Cr2O7, CrO3, H2O2) and give rise to a variety of products showing different levels of oxidation.They range from hydroxylation of the bridge methylene, e.g. in 25, to formation of the corresponding ketone, e. g. in 19, to dimerization to ethane and/or ethene derivatives as 23-24 and 20-22, respectively.The output of the oxidations is strongly dependent upon the nature of the second heteroatom in the azole ring (sulfur, oxygen or nitrogen), the oxidant, and the reaction conditions.Also the treatment of compounds 1 and 2 with the acetates of poorly azaphilic transition-metal ions promotes the dimerization couplings to the ethane or ethene products instead of leading to the formation of neutral chelates MetL2.Hydroxylation at the bridge methine in derivetives of 1 substituted at this position with a functionalized benzylic residue may result particularly easy, being simply accomplished by exposure to air.Although no mechanistic studies have been carried out on these reactions, it appears likely that a carbanionic or an enaminic intermediate is responsible for the air- and metal-promoted oxidations and oxidative couplings.
