Peptides, as neurotransmitters, neuromodulators, and hormones, influence a multitude of physiological processes by signal transduction mediated through receptors. In addition, during the last 20 years their role in the appearance or maintenance of various diseases could be unequivocally proven. Agents that can imitate or block the biological functions of bioactive peptides (agonists or antagonists, respectively) can be considered as aids for the investigation of peptidergic systems and also as therapeutic agents. The suitability of bioactive peptides as therapeutic agents was examined after preliminary pharmacological experiments. It was thereby shown that based on their pharmacological properties, for example degradation by peptidases or poor bioavailability, they could be employed as drugs in only a few cases. To solve this problem peptidomimetics, compounds that act as substitutes for peptides in their interaction with receptors, have been synthesized. In comparison with native peptides they show higher metabolic stability, better bioavailability, and longer duration of action. Peptidomimetics with antagonistic properties were also developed within the range of these investigations. As a result, new types of treatment and therapy for a series of diseases are possible. Although peptidomimetics have been developed largely by empirical methods (e.g. modification of native peptides, optimization of lead structures), methods for rational design based on investigations into the structure of peptidepeptide receptor complexes and studies of conformation energies, among others, are gradually being established.

Peptidomimetics for Receptor Ligands—Discovery, Development, and Medical Perspectives

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of atp-binding cassette transporters

Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases.

Arylglyoxals in synthesis of heterocyclic compounds.

Phosphodiesterase enzymes convert cyclic GMP and cyclic AMP to the corresponding nucleotide monophosphates. Phosphodiesterase 5 (PDE5) inhibition is now a widely accepted and efficacious therapeutic option for the treatment of erectile dysfunction in men, as a result of extensive clinical experience with sildenafil and other new PDE5 inhibitors. Research in the field continues at a substantial level to identify new, selective PDE5 inhibitors and to investigate their usefulness and activity in other areas. This review summarizes recent clinical trials with PDE5 inhibitors, advances in medicinal chemistry, and other activities and potential applications of this class of compounds.

Phosphodiesterase 5 inhibitors: current status and potential applications

Die Cycloalkano-pyridine werden hergestellt, indem man entsprechende Cycloalkano-pyridin-aldehyde
mit geeigneten metallorganischen Verbindungen oder
Wittig- oder Grignard-Reagenzien umsetzt oder Verbindungen vom Typ Cycloalkano-pyridinalkohole
mit geeigneten Bromverbindungen umsetzt, und gegebenenfalls
die funktionellen Gruppen entsprechend variiert. Die Cycloalkano-pyridine eignen sich als Wirkstoffe in Arzneimitteln, insbesondere
in Arzneimitteln zur Behandlung von Hyperlipoproteinaemia und
Arteriosklerose.

Cycloalkano-pyridine as CETP inhibitors

Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.

The invention relates to substituted chinolines of general formula (I) which are highly effective inhibitors of cholesterol ester transfer proteins (CTEP) and stimulate reverse cholesterol transfer. The inventive substances lower the LDL cholesterol level in the blood while at the same time increasing the HDL cholesterol level. Said substances can therefore be used in the treatment and prevention of hyperlipoproteinemia, hypolipoproteinimia, dyslipidiemia, hypertriglyceridemia, combined hyperlipidemia or arteriosclerosis.

5-oxysubstituted chinolines and their use as cholesterol ester transfer proteins inhibitors

The present invention relates to 7-alkyl- and cycloalkyl-substituted imidazotriazinones, to processes for their preparation and to their use as medicaments, in particular as inhibitors of cGMP-metabolizing phosphodiesterases.

7-Alkyl and cycloalkyl-substituted imidazotriazinones

The invention relates to novel arylsulphonamides of general formula (I), wherein the substituents R?1, R2, R3, R4?, A and X have the given meanings, methods for production thereof and the use thereof as antiviral agents, in particular against cytomegaloviruses.

Gunter Schmidt

Papers

Cycloalkano-pyridine as CETP inhibitors

Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.

5-oxysubstituted chinolines and their use as cholesterol ester transfer proteins inhibitors

7-Alkyl and cycloalkyl-substituted imidazotriazinones

Arylsulfonamides as antiviral agents