Computer-assisted library design

Combinatorial chemistry is able to provide the screening laboratories of pharmaceutical companies with a vast number of new chemical compounds and novel scaffolds for drug discovery. For that reason, combinatorial chemistry has rapidly become widespread among medicinal chemistry departments such that today, it is one of the most important sources of new lead structures in the drug development process [1-3]. 

To speed up the lead-finding process, the design of specialized libraries that comply with many different requirements has become increasingly important  

The resulting chemical structures should show a certain degree of drug-likeness , so that biologically active compounds can be further developed into drug candidates. 

Structural novelty is also demanded for the structures of a library. 

The region of covered chemical space should be populated steadily, without clusters or gaps. 

---

The fundamental strategy of computer-assisted library design is shown in Fig. 1. The set-up of the reaction scheme and building block selection lead to the virtual combinatorial library. Due to the virtual character of this library its size is not limited by experimental restrictions, and depends mainly on the number of available building blocks. 

Computer-Assisted Library Design 9.3.2.2 Estimation of pKp, Values... 

Computer-assisted library design can provide optimized libraries for different applications. In this example, a high overall hit-rate from an unknown library is desirable. A two-step method is used. 

The examples also show that the benefit of a theoretical investigation depends on the methods used - the choice of descriptors is especially crucial. Different descriptors must be applied for different design tasks, and all scientists who use computer-assisted library design methods should know the characteristics of basic... 

Scheme 1 Individual Steps in Computer-Assisted Library Design ...

---