Leadlike

Teague S J, A M Davis, P D Leeson and T Oprea 1999. The Design qj Leadlike Combinatorial Librarie Angewandte Chemie International Edition in English 38 3743-3748. 

Rishton, G. M. Nonleadlikeness and leadlikeness in biochemical screening. Drug Discov. Today 2002, 8, 85-96. 

Teague, S. J., Davis, A. M., Leeson, P. D Oprea, T. The design of leadlike combinatorial libraries. Angew. Chem. 

Verheij, H. J. Leadlikeness and structural diversity of synthetic screening libraries. Mol. Diversity 2006, VIO, 377-388. 

Hann, M. M., Oprea, T. I. Pursuing the leadlikeness concept in pharmaceutical... 

If multiple HTS actives of the same chemical family are to some extent leadlike (vide infra), they become a lead series, that is, structures that are amenable for further chemistry optimization and exhibit favorable patent situation [18, 19]. Lead series are further queried and derivatized in order to derive analogs with the appropriate blend of pharmacodynamic and pharmacokinetic properties. 

The concept of leadlikeness is central to drug discovery [44, 45]. As discussed earlier, the pharmaceuhcal industry, despite its century-old history, has done a poor job in documenhng the decision process, for example, why certain chemical steps were followed to reach a parhcular compound. This turns out to be a parhcularly important queshon today, since the industry is under pressure to reduce costs, increase productivity and provide high-quality leads in early preclinical discovery. Chemical aspects of the... 

By applying the results from Table 2.3 to the work presented in Tables 2.1 and 2.2, we can further examine the proportion of high-activity and low-activity molecules with leadlike properties, that is, MW < 460, LogP —4 to 4.2, ELogSw > —5, RTB < 10, RNG < 4, HDO < 5 and HAG < 9 [62]. There are 21.7% HAMs and 41% LAMs that meet the computational leadlike criteria (Table 2.4). The probability of finding HAMs in WOMBAT is rather low in the leadlike space, and is higher outside the R05-compliant space (see Hi/Lo ratios in Table 2.4). While this may not hold true across all chemical space, it does strengthen the conclusion that HAMs are decorated with... 

Tab. 2.4 The proportion of HAMs and LAMs that are leadlike and R05 compliant. The Hi/Lo ratio is obtained by dividing HAMs to LAMs and can be seen as a rough indicator of the probability of finding high-activity molecules in the chemical property space defined by leadlike and R05 criteria, respectively...

These studies consistently suggest that less complex lead structures are better to detect and exhibit a favorable optimization potential, which might influence attempts to design more leadlike [44] compound libraries for screening. They have also... 

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