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In this paper we describe the search strategies developed for docking flexible molecules to macomolecular sites that are incorporated into the widely distributed DOCK software, version 4.0. The search strategies include incremental construction and random conformation search and utilize the existing Coulombic and Lennard-Jones grid-based scoring function.(More)
We present a set of programs, DREAM+2 (Docking and Reaction programs using Efficient seArch Methods written in C++), for docking computationally generated ligands into macromolecular binding sites. DREAM++ is composed of three programs: ORIENT++, REACT++ and SEARCH++. The program ORIENT++ positions molecules in a binding site with the DOCK algorithm. Its(More)
We report a set of strategies to develop novel ligands (Structure Based and Experimental Selection of Fragments: SbE-SF). First, a docking simulation utilizing DOCK3.5 is performed in order to screen the fragment database, which was generated with the in-house program FRAGMENT++ specifically for docking simulation purposes. Although the affinity of these(More)
An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to introduce a favorable interaction with the oxy-anion hole in the catalytic triad region of fXa. This(More)
Solid-phase organic synthesis of heterocyclic compounds on solid-support has been a focus of recent investigations because of the potential applicability of these compounds toward a variety of drug targets. Among the various heterocycles, we have been especially interested in quinazoline-2,4-diones because of the wide range of their bioactivities.(More)
The first solid-phase synthesis of 1,2,4-benzothiadiazin-3-one 1,1-dioxides has been developed. Synthesis of the title compounds was achieved by the reduction of 2-nitrobenzenesulfonamides, followed by cyclization with carbonyldiimidazole. Because 1,2,4-benzothiadiazin-3-one 1,1-dioxides have been known to possess various bioactivities, this method is(More)
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