1.Crystal structure of 2,6-dimethyl-4-pyridone hemihydrate.
Nguyen DM1, Desikan V1, Golen JA2, Manke DR2. Acta Crystallogr E Crystallogr Commun. 2015 Jul 4;71(Pt 8):o533. doi: 10.1107/S2056989015012402. eCollection 2015.
The title compound (systematic name: 2,6-dimethyl-1H-pyridin-4-one hemihydrate), C7H9NO·0.5H2O, has a single planar mol-ecule in the asymmetric unit with the non-H atoms possessing a mean deviation from planarity of 0.021 Å. There is also half of a water mol-ecule present in the asymmetric unit. In the crystal, infinite (001) sheets are formed by N-H⋯O and O-H⋯O hydrogen bonds.
2.Fluorofenidone attenuates oxidative stress and renal fibrosis in obstructive nephropathy via blocking NOX2 (gp91phox) expression and inhibiting ERK/MAPK signaling pathway.
Qin J, Mei WJ, Xie YY, Huang L, Yuan QJ, Hu GY, Tao LJ, Peng ZZ. Kidney Blood Press Res. 2015;40(1):89-99.
BACKGROUND/AIMS: We evaluated the therapeutic effects of fluorofenidone (AKF-PD), a novel pyridone agent, targeting oxidative stress and fibrosis in obstructive nephropathy.
3.A selective prostaglandin E2 receptor subtype 2 (EP2) antagonist increases the macrophage-mediated clearance of amyloid-beta plaques.
Fox BM1, Beck HP1, Roveto PM1, Kayser F1, Cheng Q1, Dou H1, Williamson T2, Treanor J1, Liu H2, Jin L1, Xu G1, Ma J1, Wang S1, Olson SH1. J Med Chem. 2015 Jul 9;58(13):5256-73. doi: 10.1021/acs.jmedchem.5b00567. Epub 2015 Jun 24.
A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecule with single-digit nM binding affinity for the EP2 receptor and significantly improved microsomal stability. It was devoid of CYP inhibition and was ∼4000-fold selective against the other EP receptors. Compound 52 was shown to have good PK properties in CD-1 mice and high CNS permeability in C57Bl/6s mice and Sprague-Dawley rats. In an ex vivo assay, it demonstrated the ability to increase the macrophage-mediated clearance of amyloid-beta plaques from brain slices in a dose-dependent manner.
4.Stability of Individual Maillard Reaction Products in the Presence of the Human Colonic Microbiota.
Hellwig M1,2, Bunzel D2, Huch M2, Franz CM2, Kulling SE2, Henle T1. J Agric Food Chem. 2015 Aug 5;63(30):6723-30. doi: 10.1021/acs.jafc.5b01391. Epub 2015 Jul 24.
Maillard reaction products (MRPs) are taken up in substantial amounts with the daily diet, but the majority are not transported across the intestinal epithelium. The aim of this study was to obtain first insights into the stability of dietary MRPs in the presence of the intestinal microbiota. Four individual MRPs, namely, N-ε-fructosyllysine (FL), N-ε-carboxymethyllysine (CML), pyrraline (PYR), and maltosine (MAL), were anaerobically incubated with fecal suspensions from eight human volunteers at 37 °C for up to 72 h. The stability of the MRPs was measured by HPLC with UV and MS/MS detections. The Amadori product FL could no longer be detected after 4 h of incubation. Marked interindividual differences were observed for CML metabolism: Depending on the individual, at least 40.7 ± 1.5% of CML was degraded after 24 h of incubation, and the subjects could thus be tentatively grouped into fast and slow metabolizers of this compound. PYR was degraded by 20.