Libraries principles

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

Nicolaou, K.C. Pfefferkom, J.A. Barluenga, S. Roecker, A.J. Cao, G.-Q. (2000C) Natural product-like combinatorial libraries based on privileged structures. 3. The libraries from libraries principle for diversity enhancement of benzopyran libraries. J. Am. Chem. Soc., 122, 968-76. 

The program system COBRA [118, 119] can be regarded as a rule- and data-based approach, but also applies the principles of fragment-based (or template-based) methods extensively (for a detailed description sec Chapter 11, Sections 7.1 and 7.2 in the Handbook). COBRA uses a library of predefined, optimized 3D molecular fragments which have been derived from crystal structures and foi ce-field calculations. Each fi agment contains some additional information on... 

Ithough knowledge-based potentials are most popular, it is also possible to use other types potential function. Some of these are more firmly rooted in the fundamental physics of iteratomic interactions whereas others do not necessarily have any physical interpretation all but are able to discriminate the correct fold from decoy structures. These decoy ructures are generated so as to satisfy the basic principles of protein structure such as a ose-packed, hydrophobic core [Park and Levitt 1996]. The fold library is also clearly nportant in threading. For practical purposes the library should obviously not be too irge, but it should be as representative of the different protein folds as possible. To erive a fold database one would typically first use a relatively fast sequence comparison lethod in conjunction with cluster analysis to identify families of homologues, which are ssumed to have the same fold. A sequence identity threshold of about 30% is commonly... 

The availability of functionalized 2(lH)-pyrazinone in combination with the use of microwave accelerated solid-phase chemistry constitutes a sohd foundation for generating large libraries of compoimds suitable for medicinal chemistry. The authors have also shown that the scaffold can be further functionalized using the principles of cUck-chemistry , thereby paving the way towards highly substituted 2-pyridone structures [45-47]. 

Because of their ease of synthesis and their structural similarity to peptides, many laboratories have used peptoids as the basis for combinatorial drug discovery. Peptoids were among the first non-natural compounds used to establish the basic principles and practical methods of combinatorial discovery [17]. Typically, diverse libraries of relatively short peptoids (< 10 residues) are synthesized by the mix-and-split method and then screened for biological activity. Individual active compounds can then be identified by iterative re-synthesis, sequencing of compounds on individual beads, or indirect deduction by the preparation of positional scanning libraries. 

Stahl M. Structure-based library design. In Bohm HJ, Schneider G, editors. Virtual screening for bioactive molecules (Vol. 10 of Mannhold R, Kubinyi H, Timmerman H, editors. Methods and principles in medicinal chemistry). Wein-heim Wiley-VCH, 2000, pp. 229-64. 

McGuire, J. E. "Neoplatonism and active principles Newton and the Corpus Hermeticum." In Hermeticism and the scientific revolution, eds. R. S. Westman and J. E. McGuire, 94-142. Los Angeles Clark Memorial Library, 1977. 

Hobert H (1995) Library search - principles and applications. In Chemometrics in environmental chemistry - applications. Vol 2, part H (Vol ed J Einax), Springer, Berlin Heidelberg New York, p 1... 

Observe that to generate the reactions of Fig. 9 no information was necessary on whether such a reaction is known no database of reactions is necessary. The problems in building, updating and maintaining a reaction library are thus avoided. The formal treatment of reactions as bond and electron-shifting processes allows the generation, in principle, of all conceivable reactions, and can be seen as a method to deal freely with molecular architecture. The program s result could be a known reaction, but equally a new, as yet undiscovered reaction which could be realised in the laboratory. 

The Skraup cyclization is another reaction principle that provides rapid access to the quinoline moiety. Theoclitou and Robinson have published the preparation of a 44-member library based on the 2,2,4-trisubstituted 1,2-dihydroquinoline scaffold by the Lewis acid-catalyzed cyclization of substituted anilines or aminoheterocyc-les with appropriate ketones (Scheme 6.237) [420], The best results were obtained using 10 mol% of scandium(III) triflate as a catalyst in acetonitrile as solvent at... 

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