Challenges and Rewards in Medicinal Chemistry Targeting Cardiovascular and Metabolic Diseases

Authors

  • 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. werner.neidhart@roche.com
  • 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

DOI:

https://doi.org/10.2533/chimia.2015.407

Keywords:

Cardiovascular, High-throughput screening, Medicinal chemistry, Metabolic, Molecular design

Abstract

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.
CHIMIA Vol. 69 No. 07-08(2015): SCS Laureates and Awards & Fall Meeting 2015

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Published

2015-08-19

Issue

Vol. 69 No. 7-8 (2015): SCS Laureates and Awards & Fall Meeting 2015

Section

Scientific Articles

License

Copyright (c) 2015 Swiss Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

[1]
W. Neidhart, T. Schulz-Gasch, A. Ruf, M. Nettekoven, H. P. Märki, B. Kuhn, D. Hunziker, A. Conte, K. Amrein, J. Ackermann, A. V. Mayweg, Chimia 2015, 69, 407, DOI: 10.2533/chimia.2015.407.