Using the computer system PASS (prediction of activity spectra for substances), which predicts simultaneously several hundreds of biological activities, a training set for discriminating between drugs and nondrugs is created. For the training set, two subsets of databases of drugs and nondrugs (a subset of the World Drug Index, WDI, vs the Available Chemicals Directory, ACD) are used. The high value of prediction accuracy shows that the chemical descriptors and algorithms used in PASS provide highly robust structure-activity relationships and reliable predictions. Compared to other methods applied in this field, the direct benchmark undertaken with this paper showed that the results obtained with PASS are in good accordance with these approaches. In addition, it has been shown that the more specific drug information used in the training set of PASS, the more specific discrimination between drug and nondrug can be obtained.

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Initiated by the X-ray crystallographic data of a weakly active halothiophene benzimidazole inhibitor of serine protease factor Xa, potent achiral and nonbasic factor Xa inhibitors containing a halothiophene benzimidazole as P1 residue and tethered cyclic anilino amides as P4 ligands are synthesized. The length and nature of the linker between benzimidazole and P4 residue have influence on the potency. Variation of these parameter affords the low nanomolar inhibitors (V) and (VII). Novel anti-coagulation drugs may be obtained by improvements with respect to their physico-chemical and pharmacokinetic properties. -(MEDERSKI*, W. W. K. R.; DORSCH, D.; ANZALI, S.; GLEITZ, J.; CEZANNE, B.; TSAKLAKIDIS, C.; Bioorg. Med.

Investigations on praziquantel (PZQ) started fifty years ago by a cooperation between Bayer AG and Merck KGaA. Until today PZQ is the drug of choice for schistosomiasis in human medicine and used in many combinations with antinematode drugs in veterinary medicine. The Sm.TRPMPZQ, a Ca2+ ‐permeable transient receptor potential (TRP) channel, has been discovered as primary target of PZQ during the last decade. Furthermore, there is a short overview of routes of large‐scale synthesis of racemic and pure (R)‐PZQ. Until now racemic PZQ is used in veterinary and human medicine. In 2012 the Pediatric Praziquantel Consortium started PZQ chemistry and process development of pure (R)‐PZQ for human application. It is hoped that (R)‐PZQ will become available for pediatric use soon. The knowledge of the binding pocket of PZQ in Sm.TRPMPZQ allows to design synthesis of PZQ‐derivatives of the next generation for a target‐site directed screening. A similar screening should also be started for Fasciola hepatica TRPMPZQ.

Peptides U 0400Chlorothiophenecarboxamides as P1 Surrogates of Inhibitors of Blood Coagulation Factor Xa. -Synthesis and factor Xa inhibitory activity for 23 chlorothiophenecarboxamides bearing an amino acid and a substituted aniline are presented. Within this series (Id) is the most potent, water-soluble and orally bioavailable member. -(MEDERSKI*, W. W. K. R.; CEZANNE*, B.; VAN AMSTERDAM, C.; BUEHRING, K.-U.; DORSCH, D.; GLEITZ, J.; MAERZ, J.; TSAKLAKIDIS, C.; Bioorg. Med.

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