Challenges and Rewards in Medicinal Chemistry Targeting Cardiovascular and Metabolic Diseases
Werner Neidhart,
Tanja Schulz-Gasch,
Armin Ruf,
Matthias Nettekoven,
Hans Peter Märki,
Bernd Kuhn,
Daniel Hunziker,
Aurelia Conte,
Kurt Amrein,
Jean Ackermann,
Alexander V. Mayweg
Affiliations
Werner Neidhart
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland. [email protected]
Tanja Schulz-Gasch
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Armin Ruf
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Matthias Nettekoven
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Hans Peter Märki
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Bernd Kuhn
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Daniel Hunziker
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Aurelia Conte
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Kurt Amrein
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Jean Ackermann
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Alexander V. Mayweg
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Medicinal Chemistry, 124 Grenzacherstrasse, B 92 / 4.92, CH-4070 Basel, Switzerland
Medicinal chemistry has been transformed by major technological and conceptual innovations over the last three decades: structural biology and bioinformatics, structure and property based molecular design, the concepts of multidimensional optimization (MDO), in silico and experimental high-throughput molecular property analysis. The novel technologies advanced gradually and in synergy with biology and Roche has been at the forefront. Applications in drug discovery programs towards new medicines in cardiovascular and metabolic diseases are highlighted to show impact and advancement: the early discovery of endothelin antagonists for endothelial dysfunction (Bosentan), 11-beta hydroxysteroid dehydrogenase (11?-HSD1) inhibitors for dysregulated cellular glucocorticoid tonus (type 2 diabetes and metabolic syndrome) and non-covalent hormone sensitive lipase (HSL) inhibitors to study the scope of direct inhibition of lipolysis in the conceptual frame of lipotoxicity and type 2 diabetes.
