19788-35-3Relevant articles and documents
Auxiliary-Directed Pd-Catalyzed γ-C(sp3)-H Bond Activation of α-Aminobutanoic Acid Derivatives
Pasunooti, Kalyan Kumar,Banerjee, Biplab,Yap, Terence,Jiang, Yaojia,Liu, Chuan-Fa
, p. 6094 - 6097 (2015)
New bidentate auxiliaries derived from the isoxazole-3-carboxamide and oxazole-4-carboxamide moieties were used for Pd-catalyzed C(sp3)-H bond activation. The results show that, when placed on a primary amine compound, 5-methylisoxazole-3-carboxamide (MICA) directs Pd-catalyzed activation of inert γ-C(sp3)-H bonds for C-C bond formation. Selective and efficient arylation and alkylation of several α-aminobutanoic acid derivatives led to various γ-substituted non-natural amino acids. The MICA directing group can be conveniently removed and recovered under very mild conditions.
Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo
Vickers, Clare F.,Silva, Ana P. G.,Chakraborty, Ajanta,Fernandez, Paulina,Kurepina, Natalia,Saville, Charis,Naranjo, Yandi,Pons, Miquel,Schnettger, Laura S.,Gutierrez, Maximiliano G.,Park, Steven,Kreiswith, Barry N.,Perlin, David S.,Thomas, Eric J.,Cavet, Jennifer S.,Tabernero, Lydia
, p. 8337 - 8352 (2018/09/18)
Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.
Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles
Lindsay-Scott, Peter J.,Clarke, Aimee,Richardson, Jeffery
supporting information, p. 476 - 479 (2015/03/05)
A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.
Regioisomeric 3-, 4- and 5-aminomethyl isoxazoles: Synthesis and muscarinic activity
Dannhardt,Kiefer,Lambrecht,Laufer,Mutschler,Schweiger,Striegel
, p. 839 - 850 (2007/10/03)
A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M1 receptor subtype) and isolated guinea-pig atrium (M2 receptor subtype) and ileum (M3 receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.
