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Serotonin type 6 receptor (5-HT

Herein, a series of novel 1-((4-methoxy-3-(piperazin-1-yl)phenyl)sulfonyl)- 1H-indole derivatives were designed and synthesized via hybridization strategy of idalopirdine and SB-271046. The optimal compound C14 (K

Parkinson's disease (PD) is a common neurodegenerative disease among the elderly. Currently, monoamine oxidase B (MAO-B) inhibitors are extensively used for PD in clinics. In this work, a series of novel chiral fluorinated pyrrolidine derivatives were designed and synthesized. In vitro biological evaluations revealed that compound D5 was the most potent, selective MAO-B inhibitor (IC50 = 0.019 μM, MAO-A/MAO-B selectivity index = 2440), which was 10-fold than that of miracle drug safinamide (IC50 = 0.163 μM, MAO-A/MAO-B selectivity index = 172). It was verified that the enhanced hydrophobic interaction of D5 improved the activity against MAO-B in molecular docking study. Besides, D5 exhibited excellent metabolic properties and pharmacokinetic profiles in monkeys and rats. Moreover, D5 displayed more efficacious than safinamide in vivo models. In the MPTP-induced PD mouse model, D5 significantly alleviated DA deficits and increased the effect of levodopa on dopamine concentration in the striatum. Meanwhile, D5 produced a prominent reduction in tremulous jaw movements induced by galantamine. Accordingly, we present D5 as a novel, highly potent, and selective MAO-B inhibitor for PD therapy.

Migraine is a common neurovascular disease which has been classified as the sixth most disabling disorder. Current migraine therapy was triptans, however, riptans can cause contraction of blood vessels. Therefore, novel drugs without cardiovascular effects emerged, such as CGRP and selective 5-HT

Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Inhibition of monoamine oxidase-B (MAO-B), which is mainly found in the glial cells of the brain, may lead to an elevated level of dopamine (DA) in patients. MAO-B inhibitors have been used extensively for patients with PD. However, the discovery of the selective MAO-B inhibitor is still a challenge. In this study, a computational strategy was designed for the rapid discovery of selective MAO-B inhibitors. A series of (S)-2-(benzylamino)propanamide derivatives were designed. In vitro biological evaluations revealed that (S)-1-(4-((3-fluorobenzyl)oxy)benzyl)azetidine-2-carboxamide (C3) was more potent and selective than safinamide, a promising drug for regulating MAO-B. Further studies revealed that the selectivity mechanism of C3 was due to the steric clash caused by the residue difference of Phe208 (MAO-A) and Ile199 (MAO-B). Animal studies showed that compound C3 could inhibit cerebral MAO-B activity and alleviate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuronal loss.

Migraine is a common neurovascular disease which has been classified as the sixth most disabling disorder. Current migraine therapy was triptans, however, riptans can cause contraction of blood vessels. Therefore, novel drugs without cardiovascular effects emerged, such as CGRP and selective 5-HT1F receptor agonists. In this work, a series of pyridinylmethylenepiperidine derivatives were designed, synthesized and evaluated for their 5-HT1F receptor agonist activity. The results in vitro showed that compound C1–C6 displayed potent agonist activities compared with positive drug lasmiditan. Pharmacokinetic properties in rat indicated that 2,4,6-trifluoro-N-(6-(fluoro(1-methylpiperidin-4-ylidene)methyl)pyridin-2-yl)benzamide (C5) possessed high AUC and good bioavailability. In two rodent models of migraine, C5 significantly inhibited dural plasma protein extravasation and c-fos expression in the trigeminal nucleus caudalis. Moreover, C5 showed no effect on vasoconstriction. Through these studies, we identified C5 as a potent 5-HT1F receptor agonist for migraine therapy.

A series of novel 1-(4-(piperazin-1-yl)phenyl)pyridin-2(1H)-one derivatives were synthesized and evaluated for their serotonin (5-HT) reuptake inhibitory activity. The results in vitro indicated that most of the evaluated compounds displayed potent 5-HT reuptake inhibition. The most promising compound A20 was stable in human liver microsomes and possessed good pharmacokinetic properties. Antidepressant study in vivo of the compound A20 showed that A20 could potently antagonize the p-chloroamphetamine (PCA)-induced depletion of serotonin in hypothalamus and reduce immobility times in the rat forced swimming test (FST).

Diyne unit containing organic dyes coded as FSD105 and FSD106 were designed and synthesized to investigate their light harvesting capabilities and the DSSC performances. Through tuning the geometrical structures of dye molecules by introducing an extra ethynylene, FSD105 and FSD106 showed an obviously improved coplanar geometry, and thus the significantly bathochromic shifted absorption spectra, IPCE spectra and larger Γ values, leading to the enhancement of Jsc which guaranteed the highest η (3.82%) for FSD106-based DSSC. In order to avoid the dye aggregation, CHCl3/EtOH was adopted as the sensitizing solvents instead of CHCl3 only or CDCA as coadsorbent was added to reduce the Γ value of FSD106-based DSSC. As a result, the Jsc and the η value increased significantly. Finally, FSD106/CDCA-based DSSC showed the highest η value (4.76%), which is 1.53-fold as the previous reported FSD101-based DSSC (3.12%) by introducing an extra ethynylene to improve the molecular coplanarity.

Three new metal free organic dyes ( FSD101-103 ) were synthesized to investigate the influence of diyne unit on dye molecules. FSD101 and FSD102 with diyne unit and FSD103 with monoyne unit were applied as sensitizers in the dye-sensitized solar cells (DSSCs). The optical and electrochemical properties, theoretical studies, and photovoltaic parameters of DSSCs sensitized by these dyes were systematically investigated. By replacing the monoyne unit with a diyne unit, FSD101 exhibited broader absorption spectrum, lower IP, higher EA, lower band gap energy, higher oscillator strength, more efficient electron injection ability, broader IPCE response range and higher τ e in comparison with FSD103 . Hence, DSSC sensitized by FSD101 showed higher J sc and V oc values, and demonstrated a power conversion efficiency of 3.12%, about 2-fold as that of FSD103 (1.55%). FSD102 showed similar results as FSD101 , with a power conversion efficiency of 2.98%, despite a stronger electron withdraw cyanoacrylic acid group was introduced. This may be due to the lower efficiency of the electron injection from dye to TiO 2 and lower τ e of FSD102 than that of FSD101 . These results indicate that the performance of DSSCs can be significantly improved by introducing a diyne unit into this type of organic dyes.

A series of dialkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido](aryl) methylphosphonates derivatives were designed and synthesized. All the new compounds were identified by elemental analysis, IR, 1H NMR, 31P NMR, and MS. Their antitumor activity against KB and CNE1 cells was examined. Some of the compounds showed potential antitumor activity, which provided some hints for further study of structure modification. In particular, the compounds 6i and 6j displayed more potent cytotoxic activities against KB in comparison with 5-FU. [Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1] GRAPHICAL ABSTRACT

A series of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-pyrimidin-2-yloxy) benzoate derivatives was designed and synthesized. All new compounds were identified by elemental analysis, infrared (IR), 1H-NMR, and mass spectrometry (MS). Their herbicidal activity against a set of weed species was examined. Some of the compounds showed potential herbicidal activity, which provided some indications for further studies on structure modification. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

A novel series of ureas containing pyrimidinyl group were designed and synthesized. Some of the prepared compounds showed potential cytotoxicity against several human cancer cell lines. From the structure-activity relationships we may conclude that introduction of a sulfide bridge between phenyl and pyrimidinyl rings would be critical for their biological activities.

A novel series of chalcone derivatives containing pyrimidinyl group were synthesized and evaluated for their cytotoxic activities in vitro against various human cancer cell lines. Most of the prepared compounds showed potential cytotoxicity against several human cancer cell lines. The compound 5g displayed more potent cytotoxic activities against human cancer cell lines in comparison with Curcumin.

Compound (Ve) displays more potent cytotoxic activities against KB, MGC-803 and MCF-7 tumor cell lines than reference 5-fluorouracil.