LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.

No abstract

Excess pressure is the main driving force of oil migration in the source-reservoir system of overpressured petroliferous basins. It can reflect the change in driving force for oil migration and its influence on oil accumulation in overpressure transport layers. The drilling stem test (DST) data, well logging data, and seismic velocity data are used to describe the plane distribution of the excess pressures in the Es4s member of the Dongying Depression. Then, the values and directions of the excess pressure gradient, which can indicate oil migration and accumulation, are calculated based on the plane distribution of the excess pressure in the Es4s member of the Dongying Depression. The results suggest that overpressure is widely developed in the Es4s member of the Dongying Depression, and the excess pressure gradually decreases from the center to the edge of each sag, while the variation in the excess pressure gradient is characterized by “low-high-low” in a circular band around the sags. The excess pressure in the sag areas exceeds 15 MPa, but the excess pressure gradient is mainly between 0 and 1 MPa/km. The excess pressure in the northern steep slope zone of the Lijin sag and the northern steep slope zone of the Minfeng sag are less than 15 MPa, while the excess pressure gradient ranges from 1 to 7 MPa/km. The excess pressure in the central anticline belt and the gentle slope belt in the south of the Niuzhuang sag are between 0 and 15 MPa, and the excess pressure gradient is from 0 MPa/km to 2 MPa/km. From geochemical evidence, local oil migration directions indicated by the excess pressure gradient are consistent with those indicated by the ratio parameters of carbazole compounds in crude oil samples, indicating that the direction of the excess pressure gradient can indicate the dominant direction of oil migration driven by excess pressure, and the oil from the Es4s source rock is mainly distributed in the areas with a high excess pressure gradient or the areas with a low excess pressure gradient and low excess pressure (area II).