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Abstract: A series of small molecules consisting of a heterocyclic core flanked by two basic functionalities were synthesized and screened for in vitro affinity at the human histamine H3 receptor (hH3R). Nine of the twenty-eight compounds tested were found to possess a hH3R K i of less than 5nM and consisted of a diverse range of central hetero-aromatic linkers (pyridine, pyrazine, oxazole, isoxazole, thiazole, furan, thiophene, and pyrrole). One member of this series, (4-isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone (37), was found to be a high affinity, selective antagonist that crosses the blood-brain barrier and occupies H3 receptors after oral administration in the rat. [Copyright &y& Elsevier]

High throughput screening, using the recombinant human H3 receptor, was used to identify novel histamine H3 receptor antagonists. Evaluation of the lead compounds ultimately afforded potent, selective, orally bioavailable compounds (e.g., 38) with favorable blood–brain barrier penetration. [Copyright &y& Elsevier]

Corporations are the fastest growing source of renewable energy demand in the United States and other key markets. Corporate demand has grown from about 5% of all U.S. renewable energy in 2010 to about 13% in 2019 and could exceed 20% by 2030. Over 200 large global corporations have committed to renewable energy targets that are more aggressive than national and sub-national targets. Here, we explore how increasing corporate procurement could affect grid operations and planning. At least in the near term, rising corporate procurement will change what, where, and when renewable energy assets are deployed to the grid. Corporate procurement could increase the need for flexible grid assets, pose challenges to formal grid planning processes, and raise questions around how to effectively and equitably allocate grid costs. We explore several pathways to integrate corporate procurement into formal grid planning and maximize the value of corporate renewable energy to future grids. • Corporations are the fastest growing source of voluntary renewable energy demand. • Corporate renewable energy targets are more aggressive than utility targets. • Corporate renewable energy procurement could accelerate transition to clean grids. • Corporate procurement could affect grid operations, planning, and cost allocation. • Corporate renewable energy buyers could be engaged in formal grid planning. [ABSTRACT FROM AUTHOR]

Abstract: A series of small molecules based on a chemotype identified from our compound collection were synthesized and tested for binding affinity (IC50) at the human Neuropeptide Y Y2 receptor (NPY Y2). Six of the 23 analogs tested possessed an NPY Y2 IC50 ⩽15nM. One member of this series, JNJ 31020028, is a selective, high affinity, receptor antagonist existing as a racemic mixture. As such a synthetic route to the desired enantiomer was designed starting from commercially available (S)-(+)-mandelic acid. [Copyright &y& Elsevier]