Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524).

BAY-6096: A Potent, Selective, and Highly Water-Soluble Adrenergic α Antagonist.

After acute myocardial infarction, early reperfusion is the most effective strategy for reducing cardiac damage and improving clinical outcome. However, restoring blood flow to the ischemic myocardium can paradoxically induce injury by itself (reperfusion injury), with microvascular dysfunction being one contributing factor. α adrenergic receptors have been hypothesized to be involved in this process.

Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators.

The physiological function of free fatty acids (FFAs) has long been regarded as indirect in terms of their activities as educts and products in metabolic pathways. The observation that FFAs can also act as signaling molecules at FFA receptors (FFARs), a family of G protein-coupled receptors (GPCRs), has changed the understanding of the interplay of metabolites and host responses. Free fatty acids of different chain lengths and saturation statuses activate FFARs as endogenous agonists via binding at the orthosteric receptor site.

Potent and Selective Human Neutrophil Elastase Inhibitors with Novel Equatorial Ring Topology: in vivo Efficacy of the Polar Pyrimidopyridazine BAY-8040 in a Pulmonary Arterial Hypertension Rat Model.

Human neutrophil elastase (HNE) is a key driver of inflammation in many cardiopulmonary and systemic inflammatory and autoimmune conditions. Overshooting high HNE activity is the consequence of a disrupted protease-antiprotease balance. Accordingly, there has been an intensive search for potent and selective HNE inhibitors with suitable pharmacokinetics that would allowing oral administration in patients.

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases.

Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH).

Big pharma screening collections: more of the same or unique libraries? The AstraZeneca-Bayer Pharma AG case.

In this study, the screening collections of two major pharmaceutical companies (AstraZeneca and Bayer Pharma AG) have been compared using a 2D molecular fingerprint by a nearest neighborhood approach. Results revealed a low overlap between both collections in terms of compound identity and similarity. This emphasizes the value of screening multiple compound collections to expand the chemical space that can be accessed by high-throughput screening (HTS).

Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors.

Novel squalene synthase inhibitors are disclosed. The design, synthesis, SAR and pharmacological profile of the compounds are discussed.

Rendezvous in chemical space? Comparing the small molecule compound libraries of Bayer and Schering.

Here, we compare the entire compound collections of Bayer HealthCare and Schering AG with respect to structural identities, similarities and physico-chemical properties. We discuss possible consequences stemming from unexpected findings in light of new collaborative models in pharmaceutical research.

Total synthesis and initial structure-activity relationships of longicatenamycin A.

Natural products have provided the majority of lead structures for marketed antibacterials. In addition, they are biological guide principles to new therapies. Nevertheless, numerous "old" classes of antibiotics such as the longicatenamycins have never been explored by chemical postevolution.

Hydrophobic ion hydration and the magnitude of the dipole potential.

The magnitude of the dipole potential of lipid membranes is often estimated from the difference in conductance between the hydrophobic ions, tetraphenylborate, and tetraphenylarsonium or tetraphenylphosphonium. The calculation is based on the tetraphenylarsonium-tetraphenylborate hypothesis that the magnitude of the hydration energies of the anions and cations are equal (i.e.