Iridium-Catalyzed Reductive (3+2) Annulation of Lactams Enabling the Rapid Total Synthesis of (±)-Eburnamonine.

A reductive (3+2) annulation of lactams through iridium-catalyzed hydrosilylation and photoredox coupling with α-bromoacetic acid was developed. The iridium-catalyzed hydrosilylation of the lactam carbonyl group and subsequent elimination provide a transient cyclic enamine, which undergoes iridium-catalyzed photoredox coupling with α-bromoacetic acid in a one-pot process. The developed conditions show high functional-group tolerance and provide cyclic N,O-acetals containing a quaternary carbon center.

Synthesis of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as potent antiproliferative agents via a hybrid pharmacophore approach.

Imiquimod (1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) is efficacious in topical therapy for certain types of skin cancers. Structurally similar EAPB0203 (N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine) has been shown higher in vitro potency than imiquimod. Besides, triazole, oxadiazole, and thiadiazole rings are privileged building blocks in drug design.

Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein.

Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells.

Pharmacokinetics and pharmacodynamics of FSK0808 and Gran after single intravenous drip administration or single subcutaneous administration: comparative study in healthy Japanese adult male subjects.

FSK0808 is a recombinant human granulocyte colony-stimulating factor developed by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd.

Combination therapy of surgical tumor resection with implantation of a hydrogel containing camptothecin-loaded poly(lactic-co-glycolic acid) microspheres in a C6 rat glioma model.

We have developed a drug-loaded poly(lactic-co-glycolic acid) (PLGA) microsphere-containing thermoreversible gelation polymer (TGP) (drug/PLGA/TGP) formulation as a novel device for implantation after surgical glioma resection. TGP is a thermosensitive polymer that is a gel at body temperature and a sol at room temperature. When a drug/PLGA/TGP formulation is injected into a target site, PLGA microspheres in TGP gel localize at the injection site and do not diffuse across the entire brain tissue, and thus, sustained drug release from the PLGA microspheres at the target site is expected.

Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.

A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature.

Treatment of rat brain tumors using sustained-release of camptothecin from poly(lactic-co-glycolic acid) microspheres in a thermoreversible hydrogel.

A thermoreversible gelation polymer consisting of an aqueous solution in the sol state at room temperature and in the gel state near body temperature was examined for its use in the retention of microspheres and sustained, long-term delivery of anti-cancer drugs using a rat model of malignant glioma. The poly(lactic-co-glycolic acid) (PLGA) microspheres containing camptothecin at ratios of 1 : 33 or 1 : 50 mediated sustained release, with approximate 80% of camptothecin released after 28 d. Rats were inoculated in the brain with C6 glioma cells, followed 7 d later by injection in the tumor site with 1 : 33 and 1 : 50 PLGA microspheres dispersed in a thermoreversible gelation polymer (TGP) solution.

Temporal effects of cyclic stretching on distribution and gene expression of integrin and cytoskeleton by ligament fibroblasts in vitro.

Cyclic stretching is pivotal to maintenance of the ligaments. However, it is still not clear when ligament fibroblasts switch on expression of genes related to the mechanotransduction pathway in response to cyclic stretching. This in vitro study investigated, using ligament fibroblasts, the time-dependent changes in distribution and gene expression of beta1 integrin, the cytoskeleton, and collagens after the application of 6% cyclic stretching at a frequency of 0.

A new operative procedure using a Küntcher nail for a periprosthetic supracondylar femoral fracture after revision total knee arthroplasty: a case report.

Periprosthetic supracondylar femoral fractures after total knee arthroplasty (TKA) are difficult surgical problems. We report a case of an 84-year-old female, in which an original method was applied to treat a periprosthetic supracondylar femoral nonunion just proximal a femoral component. The new method features extending the stem of the femoral component with a Küntcher nail.