Synthesis and Modeling of Ezetimibe Analogues

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl β-lactam is described starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.

Simple Synthesis of Red Iridium(III) Complexes with Sulfur-Contained Four-Membered Ancillary Ligands for OLEDs

Phosphorescent iridium(III) complexes have been widely researched for the fabrication of efficient organic light-emitting diodes (OLEDs). In this work, three red Ir(III) complexes named Ir-1, Ir-2, and Ir-3, with Ir-S-C-S four-membered framework rings, were synthesized efficiently at room temperature within 5 min using sulfur-containing ancillary ligands with electron-donating groups of 9,10-dihydro-9,9-dimethylacridine, phenoxazine, and phenothiazine, respectively. Due to the same main ligand of 4-(4-(trifluoromethyl)phenyl)quinazoline, all Ir(III) complexes showed similar photoluminescence emissions at 622, 619, and 622 nm with phosphorescence quantum yields of 35.4%, 50.4%, and 52.8%, respectively. OLEDs employing these complexes as emitters with the structure of ITO (indium tin oxide)/HAT-CN (dipyra-zino[2,3-f,2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile, 5 nm)/TAPC (4,4′-cyclohexylidenebis[N,N-bis-(4-methylphenyl)aniline], 40 nm)/TCTA (4,4″,4″-tris(carbazol-9-yl)triphenylamine, 10 nm)/Ir(III) complex (10 wt%): 2,6DCzPPy (2,6-bis-(3-(carbazol-9-yl)phenyl)pyridine, 10 nm)/TmPyPB (1,3,5-tri(mpyrid-3-yl-phenyl)benzene, 50 nm)/LiF (1 nm)/Al (100 nm) achieved good performance. In particular, the device based on complex Ir-3 with the phenothiazine unit showed the best performance with a maximum brightness of 22,480 cd m−2, a maximum current efficiency of 23.71 cd A−1, and a maximum external quantum efficiency of 18.1%. The research results suggest the Ir(III) complexes with a four-membered ring Ir-S-C-S backbone provide ideas for the rapid preparation of Ir(III) complexes for OLEDs.

Synthesis, crystal structures, DNA interactions, and antitumor activity of two new dinuclear copper(ii) complexes with thiazole ligand

Two new dinuclear copper(ii) complexes, [Cu(ambt)2(cnba)4] (a) and [Cu(ambt)2(clba)4] (b) were synthesized with 2-amino-6-methoxybenzothiazole (ambt) as the main ligand.

ROR2 blockade as a therapy for osteoarthritis

Osteoarthritis is characterized by the loss of the articular cartilage, bone remodeling, pain, and disability. No pharmacological intervention can currently halt progression of osteoarthritis. Here, we show that blocking receptor tyrosine kinase–like orphan receptor 2 (ROR2) improves cartilage integrity and pain in osteoarthritis models by inhibiting yes-associated protein (YAP) signaling. ROR2 was up-regulated in the cartilage in response to inflammatory cytokines and mechanical stress. The main ligand for ROR2, WNT5A, and the targets YAP and connective tissue growth factor were up-regulated in osteoarthritis in humans. In vitro, ROR2 overexpression inhibited chondrocytic differentiation. Conversely, ROR2 blockade triggered chondrogenic differentiation of C3H10T1/2 cells and suppressed the expression of the cartilage-degrading enzymes a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)–4 and ADAMTS-5. The chondrogenic effect of ROR2 blockade in the cartilage was independent of WNT signaling and was mediated by down-regulation of YAP signaling. ROR2 signaling induced G protein and Rho-dependent nuclear accumulation of YAP, and YAP inhibition was required but not sufficient for ROR2 blockade–induced chondrogenesis. ROR2 silencing protected mice from instability-induced osteoarthritis with improved structural outcomes, sustained pain relief, and without apparent side effects or organ toxicity. Last, ROR2 silencing in human articular chondrocytes transplanted in nude mice led to the formation of cartilage organoids with more and better differentiated extracellular matrix, suggesting that the anabolic effect of ROR2 blockade is conserved in humans. Thus, ROR2 blockade is efficacious and well tolerated in preclinical animal models of osteoarthritis.

Preparation and Powder XRD Analysis of Tris(2,2’-bipyridine)nickel(II) Trifluoroacetate

The complex containing Ni(II)-2,2’-bipyridin (bipy)-trifluoroacetate (TFA) was prepared by direct interaction of the corresponding precursors in an aqueous solution. AAS measurement for metal content, TGA-DTA analysis and electrical conductance suggest the ionic complex of [Ni(bipy)3](CF3COO)2·6H2O. The magnetic moment of 3.13–3.17 BM indicates the paramagnetism corresponding to two unpaired electrons which is clearly higher than that of the spin only value (2.87 BM), and commonly observed due to the spin-orbit coupling in Ni(II). UV-Vis spectral property revealed the first two main ligand field bands centered at about 14200 and 18650 cm–1, which are attributed to the spin-allowed transition, 3A2g→3T2g and 3A2g→3T1g(F), respectively. The expected third band at higher energy seems to appear as a shoulder at 26500 cm–1 (378 nm), as it is masked by a strong intensity of charge transfer band centered at 31050 cm–1. The infrared spectrum exhibits mode of vibrations of the functional groups of ligand and TFA. The powder diffractogram was refined by Le Bail method and found fit as monoclinic system of space group of P21/M, with figures of merit: Rp = 3.62, Rwp = 5.76, Rexp = 3.48, goodness of fitting (GOF) 2.745 and the derived Bragg R-Factor = 0.05.

Metal Organic Frameworks of CPL-4 and CPL-5 Synthesis and Characterization under Magnetic Fields

CPL-4 and CPL-5 were synthesized with used 2,3 pyrazine dicarboxylic acid as main ligand , 4,4’-azopyridine(Apy) as linker ligand for CPL-4 and 1,2-di-(4-pyridil)ethylene(Bpe) for CPL-5 in water-ethanol(1:1) and temperature 250C. Three methods used in various reaction time and dropping method to metal ion with no stir treatment and also stirring or shaking treatment. CPL-4 have no magnetic field effect shows same XRD pattern in all synthesis method. Otherwise, CPL-5 with used method#03 shows different XRD pattern in 0T and 6T. By changing concentration of Cu2+ to 0.02 M, 6T crystal also shown different XRD pattern if compared with 6T crystal with 2 hours to 1 hours reaction time. It indicate of changing reaction between Hpzdc and Bpe with metal ion or reactivity both of ligand with metal ion induce different route under 6T. This process may effect to new crystal structure during synthesis in 6T..

Two novel neutral and ionic Ir(iii) complexes based on the same bipolar main ligand: a comparative study of their photophysical properties and applications in solution-processed red organic light-emitting diodes

A bipolar ligand design for solution-processed red Ir(iii) complex OLED.

Expression of PDCD1 (PD-1) Gene among Non-small Cell Lung Cancer (NSCLC) Patients with Real-Time PCR Application

Background: PD-L1 is the main ligand is expressed on many tumors including lung cancer and is expressed in hematopoietic cells and various leukemia. The aim of this study was to evaluate the expression of PD-1 gene and the evaluation of cancerous grades of NSCLC and its subclasses from lung cancer patients in Tehran hospitals using Real-Time PCR. Materials and Methods: A total of 35 clinical samples were collected from patients with NSCLC-derived lung cancer from three hospitals in Tehran (Khatam Hospital, Athiyah Hospital, and Masih Hospital). Of the 35 samples collected in 2017, 20% of the patients were women and 80% of them were male. The range of patients’ age spectrum was 37 - 80 years. The disease grade of the patients in this study was varied and 22 different grades among them. To investigate the PDCD-1 gene expression level, after extraction of RNA and cDNA synthesis the Real-Time PCR was done and the expression of the gene was investigated. Results: The highest grade was IIIa which contained 6 patients (17.1%). 74% of adenocarcinoma cases were in T-categories of lung cancer and 25% of patients were in grade IIIa. Patients with the grade of T3 were observed in 4 samples, 2 had adenocarcinoma and 2 with SCC with age range of 55 -62 years. The results showed that the expression of PDCD-1 increased 2.46 Fold more in patients with lung cancer than NSCLC. Conclusion: The results of this study showed that there is a significant relationship between the PDCD1 or PD-1 expression of NSCLC-type lung cancer compared with healthy individuals, and using the RT-PCR for ease and rapidity it can be proved.