Povl Krogsgaard-Larsen: A Giant in Medicinal Chemistry Research

Povl Krogsgaard-Larsen is a true giant in medicinal chemistry and without doubt the person that has had the greatest impact on this discipline in Denmark. I got to know Povl in the spring of 1970. After I had finished my chemical engineer education, I had to serve 20 months in the Danish Civil Defense corpse. The last 10 months were spent at The Royal Danish School of Pharmacy (at that time this was an independent university, today it is School of Pharmaceutical Sciences at Faculty of Health and Medical Sciences, University of Copenhagen) in The Civil Defense analytical laboratory. Povl was doing his PhD project during that period and his lab was in the same building. We met during coffee breaks, symposia, etc. After finishing my service in the Civil Defense corpse, I started as a medicinal chemist at the Danish pharmaceutical company H. Lundbeck A/S. Lundbeck was known for its antipsychotic and antidepressant drugs, and I quickly became involved in research projects aiming at discovering new, improved drugs within these classes. However, I kept a close connection to Povl and, as described below, we have over the years collaborated on a number of different projects and topics. Povl first became interested in the inhibitory neurotransmitter c-aminobutyric acid (GABA) and, during the next decade, he and his group designed a large number of compounds to map the structure–activity relationships (SAR) of GABA receptors and uptake sites. This work made the foundation of his doctoral thesis from 1980 [1]. During the following years, Povl extended his research area to also encompass the neurotransmitters acetylcholine and glutamic acid. Povl’s ambition has not been to make drugs but to explore the pharmacology and SAR of the three neurotransmitters mentioned above. He has done this by making a large number of invaluable tool compounds which facilitated not only his own research, but also the research of hundreds of researchers all over the world to whom he has generously donated his tools. Nevertheless, several compounds with drug potential have emerged over the years (the most famous example is Gaboxadol, see below). Povl’s strategy for handling the development of these lead compounds has always been a trustful collaboration with the industry, in many cases with Lundbeck. He strongly believes that patenting and development should be done by professionals, i.e. the industry. Many years ago, Lundbeck made a framework agreement with Povl that regulated such a collaboration. In essence, Lundbeck could in-license a new project if they were interested, and the new project and structures were added to the agreement in an appendix. Subsequently, the parties collaborated with further syntheses, testing, and patenting. The keyword here is trust. For Povl, it is essential that the collaboration is open, trustful and with respect for each other’s expertise, and that, at any time, information can be given without fearing that it is leaked to the outside. This type of collaboration can be very beneficial for both parties. For Lundbeck, it gave access to new CNS areas where we had no previous expertise, including substantial knowledge and technology transfer. Furthermore, through mutual PhD students and involvement in the Special Issue: In honor of Krogsgaard-Larsen.