4th EucheMs chemistry congress

wednesday, 29-Aug 2012
s719
chem. Listy 106, s587–s1425 (2012)
life sciences
Medicinal Chemistry session – iii
o - 3 3 1
deSiGn And SyntheSiS of SMALL MoLeCuLeS
AiMed At new AntiBiotiCS
f. rutJeS 1
1 Radboud University Nijmegen, Institute for Molecules and
Materials, Nijmegen, Netherlands
Since the 1960s, defeating antibacterial resistance has
mainly relied on the modification of existing antibiotics. It has
appeared, however, increasingly difficult to come up with
modifications that evade resistance without sacrificing activity
and as a result, the pressure for finding new classes of antibiotics
is higher than ever before. In this respect, the discovery of potent
new antibiotics such as platencin represented a potential
breakthrough in antibiotic research. Platencin shows
broad-spectrum Gram-positive antibacterial activity and acts on
the type II bacterial fatty acid synthesis. However, the
pharmacokinetic properties are rather poor and preclude use as an
antibiotic drug. To investigate whether platencin can be turned
into a successful drug, the development of analogues is a pivotal
first step.
In this lecture, synthetic studies directed toward the
synthesis of (–)-platencin and several analogues will be described.
Furthermore, a recently developed entirely new strategy to
disrupt bacterial fatty acid synthesis, based on pantothenic acid
derivatives, will be highlighted.
Keywords: antibiotics; total synthesis; platencin; fatty acid
biosynthesis; platensimycin;
Medicinal Chemistry session – iV
4 th EucheMs chemistry congress
o - 3 3 2
SMALL MoLeCuLe MediAted reGenerAtive
MediCine – noveL LeAd CoMPoundS for
CArdioMyoGeneSiS
M. d. MihoviLoviC 1
1 Vienna University of Technology, Institute for Applied
Synthetic Chemistry, Vienna, Austria
Regenerative Medicine is understood as one of the most
promising therapeutic approaches to alleviate a multitude of
diseases. While there is significant progress in the experimental
development of this approach related to gene therapeutic
intervention often in combination with employing embryonic stem
cells, the regulatory implications of such therapies are yet unclear
and ethical aspects represent a major obstacle in the further
development of such strategies. Hence, small molecules capable
to affect cell differentiation towards particular tissues have
received significant attention, as the prospect of employing such
agents in regenerative medicine seem highly attractive.
Within the past years we have been developing several
compounds capable to trigger differentiation of certain progenitor
cells towards particular tissues otherwise difficult to regenerate.
This particular case study aims at the development of novel lead
structures for cardiomyogenesis. We will disclose recent results
on the identification of heterocyclic scaffolds capable to
efficiently induce differentiation towards functional
cardiomyocetes starting from embryonic or progenitor cells,
ultimately leading to independently beating heart cells.
Considering the fact, that cardiac infarctation represents one of
the major death causes in the developed world, the prospect of
tissue regeneration of damaged heart muscle tissue offers a highly
innovative perspective of regaining heart function, as this organ
in not capable to functional repair on its own.
Synthetic approaches towards the individual target
compounds exploited modular strategies based on metal assisted
catalysis, in particular sequential coupling strategies (C-C, C-N,
and C-H activation). Optimization of functional decorations of
the particular heterocyclic scaffolds will be discussed in detail.
Keywords: Medicinal chemistry; Heterocycles; Drug design;
Cross-coupling;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc