Direct oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines and dihydroisoquinolines.

An efficient oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines mediated by a TEMPO oxoammonium salt has been established. A variety of electronically varied N-carbamoyl tetrahydroisoquinolines reacted with a range of alkynyl potassium trifluoroborates smoothly under mild metal-free conditions. Dihydroisoquinolines were also suitable components for the reaction.

Evaluation of WO2017098421: GSK's benzothiazine compounds as CD73 inhibitor filings.

There are considerable interests in the development of novel small-molecule CD73 inhibitors for the treatment of cancers, autoimmune diseases, precancerous syndromes, and other diseases associated with CD73 activity. Areas covered: The application claims novel substituted benzothiadiazine derivatives as CD73 inhibitors for the treatment of cancer, precancerous syndromes, AIDS, autoimmune diseases, infections, atherosclerosis, and ischemia-reperfusion injury. Many of the exemplified compounds have pIC50 values between 5 to 8.

Recent advances in the discovery of potent and selective HDAC6 inhibitors.

Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology.

Oxidative C-H functionalization of N-carbamoyl 1,2-dihydroquinolines.

A modular and efficient method for the synthesis of α-substituted 1,2-dihydroquinolines is described. Under mild metal-free conditions, readily available N-carbamoyl 1,2-dihydroquinolines undergo oxidative C-H alkynylation, alkenylation, and allylation with a range of potassium trifluoroborates using TEMPO oxoammonium salt as an oxidant.

Recent Research Advances in Selective Matrix Metalloproteinase-13 Inhibitors as Anti-Osteoarthritis Agents.

Matrix metalloproteinase-13 (MMP-13) plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). The subtle differences between the S1' loop of MMP-13 and that of other MMPs offer a structural base for the design of selective MMP-13 inhibitors to mitigate the unperceived risk associated with inhibiting other MMP isoforms. In this review, we summarize zinc-binding and non-zinc-binding selective MMP-13 inhibitors.

Studies on pharmacokinetics and bioavailability of aminophylline in partridge chickens.

Veterinary medicine plays a significant role in the development of animal husbandry. Drugs residual in food would follow the food-chain coming into human body, which might bring hidden dangers to people. Chicken is the prime source of meat food, whose quality is important for our life and health.

Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents.

Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity, cell survival, and prevention tumorigenesis. Three pathways are responsible for the repair of DNA DSBs: homologous recombination (HR), single strand annealing (SSA) and non-homologous end joining (NHEJ). DNA-dependent Protein Kinase (DNA-PK), the key component of the NHEJ pathway, becomes an important target for cancer therapy.

Developments of kinesin spindle protein inhibitors as antitumor agents based on the five-membered heterocycle scaffolds.

Kinesin spindle protein (KSP) plays an essential role in centrosome separation and formation of the bipolar mitotic spindle. Its exclusive involvement in the mitotic spindle of proliferating cells presents an opportunity for developing new anticancer agents with reduced side effects relative to antimitotics that target tubulin. Small molecule KSP inhibitors have demonstrated their potential as novel antimitotic agents.

Recent developments of 19-nor-1,25-dihydroxyvitamin D3 analogues.

The vitamin D hormone, 1α,25-dihydroxyvitamin D3 [1,25-(OH)2 D3 ], exerts its hormonal effects predominantly on intestine, bone, and kidney, where it plays a crucial role in calcium and phosphorus homeostasis and bone mineralization. In addition to its classical actions, 1,25(OH)2 D3 exerts pleiotropic effects in a wide variety of target tissues and cell types, often in an autocrine/paracrine fashion. These biological activities of 1,25(OH)2 D3 have suggested a multitude of potential therapeutic applications for the vitamin D hormone in the treatment of hyperproliferative disorders (e.

Enhancing effects of different dosages of borneol on pharmacokinetics of salvanic acid B after oral administration to rats.

The main purpose of this study was to illustrate the effect of borneol on pharmacokinetics of salvianolic acid B (SalB) in rats after oral administration of SalB with different doses of borneol. The concentrations of SalB in rat plasma were determined by an established and validated LC-MS/MS method. Our data showed that when 20, 40, and 80 mg kg⁻¹ of borneol were orally administrated with SalB at 50 mg kg⁻¹, C (max) of SalB was increased by 18.

Pharmacokinetics of vertilmicin, a novel aminoglycoside antibiotic, in rats and dogs.

The pharmacokinetics of vertilmicin was investigated in rats and dogs following intramuscular or intravenous administration of vertilmicin. Following a single administration of an intramuscular dose, serum concentrations of vertilmicin peaked at 0.63 h in rats and 0.

The effects of salvianolic acid B from radix salvia miltiorrhizae on the oral pharmacokinetics of metoprolol and metoprolol acid in rats.

The present study aimed to investigate the effects of salvianolic acid B (SalB) isolated from Radix Salvia miltiorrhizae on the oral pharmacokinetics of metoprolol (MET) and metoprolol acid (META) in rats. The pharmacokinetic parameters of MET and META were measured after oral (15 mg/kg) administration of MET in rats in the presence and absence of SalB. Compared to the control given MET alone, with the concurrent administration of SalB (50 mg/kg), the AUC and C(max) of MET increased by 51.

[Observation on therapeutic effect of medicinal moxa stick moxibustion for treatment of tinea pedis].

Objective: To observe therapeutic effect of using medicinal moxa stick moxibustion for treatment of tinea pedis.

Methods: One hundred and forty-four cases were randomly divided into a medicinal moxa stick group (MMS), a moxa stick group (MS) and a Nitramisole cream group (NC) (n = 48 in each group). The moxibustion method was applied in both MMS group and MS group.