Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Synthesis of the Antibiotic Precursor Thiazolyl‐7‐Aminocephalosporanic Acid in a Microstructured Flow System

The synthesis of thiazolyl‐7‐aminocephalosporanic acid, a pharmaceutical precursor of the β‐lactam antibiotic drug cefodizime, could be successfully realized in a continuous microstructured flow system. This was accomplished by changing the process window from batch, having a reaction temperature of 60 °C with a reaction time of 1 h, to a flow system at temperatures > 100 °C and reaction times of several minutes. The space‐time yield could be increased by a factor of 130.     

Gender and support for creativity at work

Although innovation is vital for the success of organizations, many may not be capitalizing on the creativity of all workers. Gender bias in attributions of creativity may lead to an imbalance in the extent to which organizations support the creativity of men and women. Because organizational support for creativity is positively associated with creative outcomes, this may undermine the creativity of women in the workplace. To determine if gender influences creative workplace behavior through support for creativity, conditional process models were used to analyze the survey responses and external employment data of workers (N = 14,590) across industries in the US. Our analyses demonstrate that men report greater support for creativity in the workplace than women, and greater support for workplace creativity leads to more frequent creative workplace behaviors. The proportion of women employed in an industry influences this relationship, such that differences between men and women become smaller as the proportion of women in an industry increases. However, the level of creativity required in an occupation does not influence the relationship between gender and creativity. The theoretical and practical implications of these results are discussed.     

Effect of additives on the melt rheology and thermal degradation of poly[(R)‐3‐hydroxybutyric acid]

Thermal degradation of poly[(R)−3‐hydroxybutyric acid] (PHB) during melt mixing results in random chain scission that produces shorter polymer chains containing crotonic and carboxyl end groups. One way of preventing this serious reduction of molar mass is to add agents that react with at least two of the newly generated end groups. Different types of commercially available additives known to react with carboxyl group, namely bis(3,4‐epoxycyclohexylmethyl) adipate (BECMA), 2,2'‐bis(2‐oxazoline) (BOX), trimethylolpropane tris(2‐methyl‐1‐aziridinepropionate) (PETAP), triphenyl phosphate (TPP), tris(nonylphenyl) phosphate (TNPP), polycarbodiimide (PCDI), and poly(methyl metharylate‐co‐glycidyl methacrylate) (GMA.MMA) were mixed with PHB by cocasting from solution in chloroform. Dynamic rheology as well as measurements of molar masses before and after dynamic analysis was used to evaluate the effect of the additives on the melt stability of PHB. Measurements of the dynamic shear modulus and the molar mass of molten PHB with the additives PCDI and GMA.MMA showed a minor improvement on the thermal stability. Furthermore, TPP and TNPP did not affect the thermal stability of PHB, whereas the presence of BECMA, BOX, and PETAP gave a strong decrease of the dynamic modulus compared with neat PHB. © 2014 The Authors Journal of Applied Polymer Science Published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41836.