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In the fight against doping, creating a level playing field across all sports is very challenging from a legal perspective. A harmonized approach presupposes first and foremost a supreme regulatory authority on a global level. This task cannot be attributed to the public sector, because there is no supranational authority of public international law capable of dealing with it. Thus, responsibility has to be assumed by a private law entity. This in turn requires complicated contractual agreements by which duties and responsibilities are transferred from the individual to the national level and from there to the top of the pyramid. In practice, this process is not only difficult and cumbersome, it also leads to an accumulation of power at the top of the sports pyramid that must be contained by organizational checks and balances, such as access to justice and the rule of law, accountability, transparency, and possibilities for the respective stakeholders to partake in the decision-making process. The weighting of all these different aspects is demanding and further complicated by the regulatory reach of the various national lawmakers. Since national laws differ considerably and a harmonized legislative approach is nowhere near in sight, a global approach in the fight against doping must push back national laws and legal concepts as much as possible. The purpose of this chapter is to give an overview on all these legal challenges.

Dose-response curves of angiotensin I (AI, 1.0–1000.0 pmol) and angiotensin II (AII, 1.25–1250.00 pmol) were obtained in isolated rat hearts subjected to control conditions, mild hypoxia (PO2 = 145 mm Hg), reoxygenation, ischemic (perfusion pressure = 35 mm Hg) and reperfusion. Both AI and All caused dose-dependent coronary vasoconstriction in control hearts, with a maximal reduction of coronary flow (CF) of 26 ± 3 and 27 ± 2%, respectively. The effects of both AI and AII were substantially attenuated during hypoxia, but were fully restored upon reoxygenation. During ischemia, the effect of AII was unaltered while the effect of AI was enhanced compared to the control (P < 0.05). This enhancement was reversible on reperfusion. Cardiac conversion of AI, calculated from ED50 values for AI and AII, was significantly increased during ischemia (P < 0.05). Infusion of saralasin (0.5–5.0 μg/min) did not increase CF in any of the groups. We conclude that (1) the coronary vasoconstrictive effect of AII is preserved in ischemia but attenuated in hypoxia and (2) cardiac conversion of AI to AII is enhanced in hearts injured by ischemia.

The search for new active molecules with novel modes of action and desirable physical properties is an ongoing endeavour. This publication describes the follow-up chemistry of a biological hit discovered in the screening system of Novartis Crop Protection, the legacy agrochemical parent of Syngenta Crop Protection. This chemistry was optimized through classical synthetic methods and automated parallel synthesis with coverage of important physical properties such as lipophilicity or Clog P and solubility. Preliminary biological activity from the greenhouse and field data with symptomology is presented.