Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue.

[A Patient with Recurrent Invasive Thymoma Obtaining Long-Term Survival by Chemotherapy with Amrubicin Alone as the Third Treatment].

The patient was a 68-year-old woman. She was diagnosed with invasive thymoma 12years prior and underwent chemoradiotherapy( adriamycin, cisplatin, vincristine, and cyclophosphamide: ADOC)plus radiation exposure(62G y). After 11 years, the disease relapsed.

[A Case in Which Toxic Epidermal Necrosis Developed during Treatment with the Immune Checkpoint Inhibitor Pembrolizumab for Recurrent Patients Following Lung Cancer Surgery].

The patient was a 66-year-old male. Following surgery for pulmonary adenocarcinoma in the upper right lobe and adjuvant chemotherapy, the patient relapsed. We carried out treatment using the immune checkpoint inhibitor pembrolizumab (KEYTRUDA®)for high expression of PD-L1.

[A Case in Which Good Control of Carcinomatous Serositis Was Achieved Using Chemotherapy Including Albumin-Bound Paclitaxel(Nab-PTX)for Advanced-Stage Pulmonary Adenocarcinoma Exhibiting Carcinomatous Pleurisy and Carcinomatous Pericarditis].

The subject was a 63-year-old man. The patient was transported by ambulance to the hospital because of dyspnea caused by carcinomatous pleurisy and carcinomatous pericarditis, after which pericardial drainage was performed; however, Staphylococcus aureus bacteremia arose as a complication. Adequate control of carcinomatous serositis was achieved usingchemotherapy, includingalbumin -bound paclitaxel(nab-PTX), which is a nanoparticle formulation bindinghuman serum albumin and paclitaxel, in combination with 1 course of antibiotics.

Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist.

Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. The compound also showed in vivo efficacy after oral dosing. Therefore, compound 39 was selected to undergo further studies as a clinical candidate.

Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists.

The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency and selectivity against other opioid receptors and hERG potassium channel.

A novel class of cycloalkano[b]pyridines as potent and orally active opioid receptor-like 1 antagonists with minimal binding affinity to the hERG K+ channel.

A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5 H-cyclohepta[ b]pyridine-9-ol ( (-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K (+) channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K (+)channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.

Design, synthesis, and structure-activity relationship study of a novel class of ORL1 receptor antagonists based on N-biarylmethyl spiropiperidine.

Based on reported structures, a focused library of biarylmethyl bound to the nitrogen atom of spiropiperidine was designed. Systematic modifications allowed the discovery of a synthetically feasible and highly potent ORL1 antagonist 37, 1'-{[1-(3-chloropyridin-2-yl)-1H-pyrazol-4-yl]methyl}-3H-spiro[2-benzofuran-1,4'-piperidine], which exhibits excellent selectivity to mu, kappa, and human ether-a-go-go related gene potassium channel.

Asymmetric total syntheses of (+)-cheimonophyllon e and (+)-cheimonophyllal.

The highly enantiocontrolled total syntheses of natural (+)-cheimonophyllon E (5) and (+)-cheimonophyllal (6), biologically intriguing oxygenated bisabolane-type sesquiterpenoids, have been completed. The present synthetic strategy featured the use of an asymmetric aldol-type reaction for preparing in the first synthetic step an optically active 6-C-substituted 3-methyl-2-cyclohexenone derivative. Thus, a Mukaiyama aldol reaction of 1-methyl-3-silyloxy-1,3-cyclohexadiene 31 with alpha,beta-unsaturated aldehyde 11 in the presence of a chiral (acyloxy)borane (CAB)-type Yamamoto catalyst 33 proceeded with high levels of both diastereo- and enantioselectivities.