Stereochemical properties of quazepam and its affinity for the GABA receptor.

C9-methylated quazepam 1 was prepared, and its physicochemical properties were investigated. The atropisomers of 1 were isolated as (aR, aS) and (aS, aR) isomers. Their absolute configurations were determined based on ECD spectra in comparison with those calculated using the time-dependent density functional theory.

Fentanyl-Type Antagonist of the μ-Opioid Receptor: Important Role of Axial Chirality in the Active Conformation.

In recent years, synthetic opioids have emerged as a predominant cause of drug-overdose-related fatalities, causing the "opioid crisis." To design safer therapeutic agents, we accidentally discovered μ-opioid receptor (MOR) antagonists based on fentanyl with a relatively uncomplicated chemical composition that potentiates structural modifications. Here, we showed the development of novel atropisomeric fentanyl analogues that exhibit more potent antagonistic activity against MOR than naloxone, a morphinan MOR antagonist.

Safety and efficacy of neoadjuvant chemotherapy with paclitaxel, carboplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma.

Background: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen.

Multicenter prospective phase II trial of concurrent chemoradiotherapy with weekly low-dose carboplatin for cisplatin-ineligible patients with advanced head and neck squamous cell carcinoma.

Background: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible.

Methods: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR).

Treatment Outcome in Head and Neck Cancer With Distant Metastasis at Initial Diagnosis.

Objective: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease.

Stereochemistry of -Acyl-5-dibenzo[,]azepin-7(6)-ones.

The stereochemical properties of -acyl-5-dibenzo[,]azepin-7(6)-ones (-), which inhibit potassium channels in T cells, were examined by freezing their conformational change due to 4-methyl substitution. -Acyl-5-dibenzo[,]azepin-7(6)-ones exist as pairs of enantiomers [(a, a), (a, a)], and each atropisomer is separable at room temperature. An alternate procedure for preparing 5-dibenzo[,]azepin-7(6)-ones involves the intramolecular Friedel-Crafts cyclization of -benzyloxycarbonylated biaryl amino acids.

Chemoradiotherapy with 3-weekly CDDP 80 mg/m for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study.

Objective: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m administered once every three weeks, although cisplatin 80 mg/m is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m.

Methods: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m was performed in 47 patients between April 2015 and December 2016 at four centers in Japan.

Head and neck small-cell carcinoma: A multicenter study of 39 cases from 10 institutions.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC.

Materials And Methods: This study involved 47 patients with HNSmCC from 10 participating institutions.

Atropisomeric Properties of N-Alkyl/Aryl 5H-Dibenz[b,f]azepines.

The atropisomeric properties of N-alkyl and N-aryl 4-substituted 5H-dibenz[b,f]azepines were investigated. The N-alkylation and N-arylation of 4-Cl or 4-Me substituted compounds was performed; however, none of the atropisomers produced were separated by chiral HPLC. Notably, we observed that the rotation of the four axes (ax.

Axial chirality and affinity at the GABA receptor of triazolobenzodiazepines.

Triazolobenzodiazepines substituted with a methyl group at the C1- and C10-positions and chloro group at C2' of pendant-phenyl were prepared and their physicochemical properties were investigated. The atropisomers of 1,10-disubstituted triazolobenzodiazepines, 1d and 1f, were isolated as (aR, aS) and (aS, aR) isomers. Their absolute configurations were determined on the basis of CD spectra in comparison with those of stereochemically defined 9-methyl-1,4-benzodiazepin-2-ones.

Treatment Outcome of External Auditory Canal Carcinoma: The Utility of Lateral Temporal Bone Resection.

We examined the role of lateral temporal bone resection (LTBR) in the treatment of external ear canal (EAC) carcinoma between 2007 and 2018. The estimated 3-year disease-free survival (DFS) and disease-specific survival (DSS) according to the tumor stage and treatments were investigated in 36 patients with EAC squamous cell carcinoma. T stage classification according to the University of Pittsburgh staging system was as follows: 14 patients in T1, four patients in T2, nine patients in T3, and nine patients in T4.

Impaired secretion of carboxyl-terminal truncated factor VII due to an F7 nonsense mutation associated with FVII deficiency.

Introduction: Factor VII (FVII) is a vitamin K-dependent glycoprotein secreted into the blood circulation from hepatic cells. We investigated the molecular basis of the congenital FVII deficiency found in a Japanese patient.

Materials And Methods: We analyzed the F7 gene of the patient, who was diagnosed with a FVII deficiency at pregnancy.

Quantitative measurements of oxidative stress in mouse skin induced by X-ray irradiation.

To find efficient methods to evaluate oxidative stress in mouse skin caused by X-ray irradiation, several markers and methodologies were examined. Hairless mice were irradiated with 50 Gy X-rays and skin homogenates or skin strips were prepared. Lipid peroxidation was measured using the skin homogenate as the level of thiobarbituric acid reactive substances.

Ultrasonic plastic welding using fundamental and higher resonance frequencies.

Ultrasonic plastic welding using fundamental and higher resonance frequency vibrations simultaneously was studied. Using higher frequency, welding characteristics is improved due to the larger vibration loss of plastic materials. The 26 kHz welding tip vibrates in maximum velocity of over 4.