Discovery of a novel series of GPR119 agonists: Design, synthesis, and biological evaluation of N-(Piperidin-4-yl)-N-(trifluoromethyl)pyrimidin-4-amine derivatives.

We undertook an optimization effort involving propan-2-yl 4-({6-[5-(methanesulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate 1, which we had previously discovered as a novel G protein-coupled receptor 119 (GPR119) agonist. To occupy a presumed hydrophobic space between the pyrimidine and piperidine rings in interaction with GPR119, we replaced the linker oxygen with nitrogen. Subsequently, the introduction of a substituent at the bridging nitrogen atom was explored.

Discovery of a novel series of indolinylpyrimidine-based GPR119 agonists: Elimination of ether-a-go-go-related gene liability using a hydrogen bond acceptor-focused approach.

We previously identified a novel series of indolinylpyrimidine derivatives exemplified by 2 in Figure 1, which is an indoline based derivative, as potent GPR119 agonists. Despite the attractive potency of 2, this compound inhibited the human ether-a-go-go-related gene (hERG) K channel. We elucidated crucial roles of the methylsulfonyl group of 2 in its interaction with the hERG channel and the GPR119 receptor, presumably as a hydrogen bond acceptor (HBA).

Visible-Light-Activated Response Originating from Carrier-Mobility Modulation of NO Gas Sensors Based on MoS Monolayers.

Some gas sensors exhibit significant increases in their sensitivity and response/recovery rates under light illumination. This photoactivation of the gas response is considered a promising alternative to conventional thermal activation, which requires high power consumption. Thin layers of molybdenum disulfide (MoS) are known to exhibit an effective photoactivated gas response under visible light.

Bias- and Gate-Tunable Gas Sensor Response Originating from Modulation in the Schottky Barrier Height of a Graphene/MoS van der Waals Heterojunction.

We report on the gas-sensing characteristics of a van der Waals heterojunction consisting of graphene and a MoS flake. To extract the response actually originating from the heterojunction area, the other gas-sensitive parts were passivated by gas barrier layers. The graphene/MoS heterojunction device demonstrated a significant change in resistance, by a factor of greater than 10, upon exposure to 1 ppm NO under a reverse-bias condition, which was revealed to be a direct reflection of the modulation of the Schottky barrier height at the graphene/MoS interface.

Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors.

Objective: Placental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs.