Pharmacophore-based design

Williams CGRP Potency, cellular, PK Pharmacophore-based design [52]... 

M., Giannaccini, G., Maccari, L., Manetti, F., Strappaghetti, G., Tafi, A., Corsano, S. eq-Adrenoceptor antagonists. 4. Pharmacophore-based design, synthesis and biological evaluation of new imida-zo-, benzimidazo-, and indoloarylpipera-zine derivatives. J. Med. Chem. 2002, 45, 3603-3611. 

Barreca ML, Ferro S, Rao A et al (2005) Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors. J Med Chem 48 7084—7088... 

In Silico Techniques are shown in Boxes viz, structure-based designing Pharmacophore-based designing and combinatorial Library generation and virtual screening/designing]... 

Knowledge-Based Design Approaches to Lead Optimization 4.3.3.1 Ligand and Pharmacophore-Based Design... 

Historically, ligand structure-based design has been the most widely used approach to the design of target-directed chemical libraries. Methods that start from hits or leads are among the most diverse, ranging from 2D substructure search and similarity-based techniques to analysis of 3D pharmacophores and molecular interaction fields (Fig. 15.2). 

Clement OO, Mehl AT. HipHop pharmacophores based on multiple common-feature alignments. In Gtiner OF, editor. Pharmacophore perception, development and use in drug design. La Jolla International University Line, 2000. p. 69-84. 

The phase transition boundaries (phase envelope) of adamantane need to be investigated and constmcted. Predictable and diverse geometries are important features for molecular self-assembly and pharmacophore-based dmg design. Incorporation of higher diamondoids in solid-state systems and polymers should provide high-temperature stability, a property already found in polymers synthesized from lower diamondoids. 

The design of new analogs based on pharmacophore models is complementary to structure-based design. This method may be used even where structural information is available, but is also of use for targets where structural information is not... 

Clement, O.O. and Mehl, A.T. (2000) HipHop pharmacophores based on multiple common-feature alignments, in Pharmacophore Perception, Development, and Use in Drug Design (ed. O.F. Giiner), International University Line, La Jolla, CA, pp.69-84. 

Quantitative Structure-Activity Relationship models are used increasingly in chemical data mining and combinatorial library design [5, 6]. For example, three-dimensional (3-D) stereoelectronic pharmacophore based on QSAR modeling was used recently to search the National Cancer Institute Repository of Small Molecules [7] to find new leads for inhibiting HIV type 1 reverse transcriptase at the nonnucleoside binding site [8]. A descriptor pharmacophore concept was introduced by us recently [9] on the basis of variable selection QSAR the descriptor pharmacophore is defined as a subset of... 

Eksterowicz, J. E., Evensen, E., Lemmen, C., et al. (2002) Coupling structure-based design with combinatorial chemistry application of active site derived pharmacophores with informative library design. J. Mol. Graph. Model. 20, 469-477. 

Afifymax s thiolacyl library (Fig. 1.9) and Pharmacopeia s statine library (Fig. 1.10) are pharmacophore-based libraries however, their design is different. In the former library, a pool of advanced library intermediates are derivatized with the pharmacophore (thiolacylation) as the final step in library construction, while in the latter library the pharmacophore (statine) is derivatized with synthons as part of library construction. 

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