Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HT2B/5HT2C Serotonin Receptor Antagonists

Adenosine derivatives developed to activate adenosine receptors (ARs) revealed micromolar activity at serotonin 5HT(2B) and 5HT(2C) receptors (5HTRs). We explored the structure activity relationship at 5HT(2)Rs and modeled receptor interactions in order to optimize affinity and simultaneously reduce AR affinity. Depending on N-6 substitution, small 5'-alkylamide modification maintained 5HT(2B)R affinity, which was enhanced upon ribose substitution with rigid bicyclo [3.1.0]-hexane (North (N)-methanocarba), e.g., N-6-dicydopropylmethyl 4'-CH2OH derivative 14 (K-i 11 nM). 5'-Methylamide 23 was 170-fold selective as antagonist for 5HT(2B)R vs 5HT(2C)R. 5'-Methyl 25 and ethyl 26 esters potently antagonized 5HT(2)Rs with moderate selectivity in comparison to ARs; related 6-N,N-dimethylamino analogue 30 was 5HT(2)R-selective. 5' position flexibility of substitution was indicated in 5HT(2B)R docking. Both 5'-ester and 5'-amide derivatives displayed in vivo t(1/2) of 3-4 h. Thus, we used G protein-coupled receptor modeling to repurpose nucleoside scaffolds in favor of binding at nonpurine receptors as novel 5HT(2)R antagonists, with potential for cardioprotection, liver protection, or central nervous system activity

A Web Service Interface for a Distributed Measurement System Based on Decentralized Sharing Network

The Web Service technology has increased in importance in these years. Accessing to remote resources without knowledge about physical implementation and with a reduced hardware requirement is the main goal of new portable device. The use of Web Service technology allows clients to create a standard interface to access to the measurement service published by the server. In low cost multipoint distributed measurement systems, the measurement services are provided by Smart Web Sensors. A new concept of distributed measurement system arises from the possibility to fuse all services with the same functionality in a single user-transparent service: the response of distributed services network to a user request gives a complete vision of the service by collecting results from any Smart Web Sensor in the network. So, in this paper the development of a multipoint distributed measurement system, based on the peer-to-peer Gnutella network with Web Service interface, is presented