Gender Gaps in the Measurement of Public Opinion About Homosexuality in Cross-national Surveys: A Question-Wording Experiment

Measures of attitudes towards homosexuality in cross-national studies have received criticism for not being ‘gender-sensitive’. The current study used a split-ballot design allowing for separate analyses of the attitudes towards ‘gay men and lesbian women’, ‘gay men’, and ‘lesbian women’ in a pooled sample of 3,381 participants from Great Britain, Hungary, and Portugal. Analyses controlling for sociodemographics showed that differences in attitudes towards male and female targets were generally small and did not interact with the gender of the rater. In addition, results showed that men’s attitudes towards homosexuality were more strongly related to their gender ideology than women’s attitudes. Implications of these findings for cross-national studies measuring attitudes towards homosexuality are discussed

Highly Chemo- and Regioselective Vinylation of <i>N</i>‑Heteroarenes with Vinylsulfonium Salts

An efficient chemo- and regioselective <i>N</i>-vinylation of <i>N</i>-heteroarenes has been developed using vinylsulfonium salts. The reaction proceeded under mild and transition-metal-free conditions and consistently provided moderate to high yields of vinylation products with 100% <i>E</i>-stereoselectivity. This reaction is also highly chemoselective, and compatible with a variety of functional groups, such as -NHR, -NH₂, -OH, -COOH, ester, etc

Palladium-Catalyzed Difluoromethylation of Aryl Chlorides and Triflates and Its Applications in the Preparation of Difluoromethylated Derivatives of Drug/Agrochemical Molecules

A palladium-catalyzed difluoromethylation of a series of aryl chlorides and triflates under mild conditions was described. A variety of common functional groups were tolerated. In addition, by using this protocol, several drug molecules containing an aryl chloride unit were successfully difluoromethylated, thus enabling medicinal chemists to rapidly access novel drug derivatives with potentially improved properties via late-stage functionalization

C–H Bond Functionalization of Tetrahydropyridopyrimidines and Other Related Hetereocycles

A novel and efficient 2-step method for the functionalization of the C–H bond adjacent to the amino group of tetrahydropyridopyrimidine (THPP) is reported herein. The reaction features mild conditions and excellent tolerance of a wide range of functional groups. Moreover, this method is applicable to tetrahydroisoquinolone (THIQ), which provides a useful supplement to literature method. This method gives chemists a new tool to functionalize a C–H bond at late stage and may find applications in both synthetic organic and medicinal chemistry

Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors

A novel series of piperazinylquinoline derivatives were discovered as respiratory syncytial virus (RSV) fusion inhibitors by the ligand-based screening approach. Among 3,000 hits, 1-amino-3-[[2-(4-phenyl-1-piperidyl)-4-quinolyl]­amino]­propan-2-ol (<b>7</b>) was proven to be active against the RSV long (A) strain. The anti-RSV activity was improved by converting piperidine to benzylcarbonyl substituted piperazine. The basic side chain was also found to be crucial for anti-RSV activity. The selected analogues, <b>45</b> and <b>50</b>, demonstrated anti-RSV activities up to EC₅₀ = 0.028 μM and 0.033 μM, respectively. A direct anti-RSV effect was confirmed by a plaque reduction assay and a fusion inhibition assay. Both <b>45</b> and <b>50</b> showed promising DMPK properties with good oral bioavailability, and could potentially lead to novel therapeutic agents targeting the RSV fusion process

Structure-Based Design and Synthesis of Potent Cyclic Peptides Inhibiting the YAP–TEAD Protein–Protein Interaction

The YAP–TEAD protein–protein interaction (PPI) mediates the oncogenic function of YAP, and inhibitors of this PPI have potential usage in treatment of YAP-involved cancers. Here we report the design and synthesis of potent cyclic peptide inhibitors of the YAP–TEAD interaction. A truncation study of YAP interface 3 peptide identified YAP^84–100 as a weak peptide inhibitor (IC₅₀ = 37 μM), and an alanine scan revealed a beneficial mutation, D94A. Subsequent replacement of a native cation−π interaction with an optimized disulfide bridge for conformational constraint and synergistic effect between macrocyclization and modification at positions 91 and 93 greatly boosted inhibitory activity. Peptide <b>17</b> was identified with an IC₅₀ of 25 nM, and the binding affinity (<i>K</i>_d = 15 nM) of this 17mer peptide to TEAD1 proved to be stronger than YAP^50–171 (<i>K</i>_d = 40 nM)

Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo­[1,5-a]­pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos­(t)­ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration

Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo­[1,5-a]­pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos­(t)­ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration

Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists

Elaboration of the oxazolidinedione series led to replacement of the exocyclic amides with substituted benzimidazoles. The structure–activity relationship (SAR) exploration resulted in the discovery of potent and selective nonsteroidal mineralocorticoid receptor (MR) antagonists with significantly improved microsomal stability and pharmacokinetic (PK) profile relative to the HTS hit <b>1a</b>. One compound <b>2p</b> possessed comparable efficacy as spironolactone (SPL) at 100 mg/kg (p.o.) in the rat natriuresis model. As such, this series was validated as a lead series for further optimization