Gold Standard for Drug Molecules

16 OCTANOL-WATER logPw, logP, AND log 74 GOLD STANDARD FOR DRUG MOLECULES 

About 300 values of octanol-water log PN, log P1, and logD74 of drugs and some agrochemicals are listed in Table 4.1. These have been critically selected to represent high-quality results. Most of these constants have been determined at Sirius or pION since 1991, with many personally determined by the author. 

TABLE 4.1 Critically Selected Experimental logP v, logp an(j iog/)74 of Drug Molecules0 

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The blue book compilations [154-158] are probably the most comprehensive sources of ionization constants collected from the literature (up to the end of 1970s). These are recommended for experts in the field. On the other hand, the red books contain critically selected values [159]. The six-volume set has been put into electronic form in cooperation with NIST (National Institute of Standards and Technology), and is available at a very reasonable price [160]. A two-volume set of critically determined constants is available from Sirius Analytical Instalments Ltd., and covers molecules of particular interest to the pharmaceutical community [161,162]. In Section 3.8 at the end of this chapter, a list of gold standard pKa values of mostly drug-like molecules is presented (see Table 3.1), with many of the values determined by the author since the early 1970s. 

Figure 1.12 Determining the properties of drug molecules. Drug molecules may have their properties ascertained by either experimental or theoretical methods. Although experimental methods, especially X-ray crystallography, are the gold standard methods, calculational approaches tend to be faster and do provide high qnality information. Nonempirical techniques, such as ab initio quantum mechanics calcnlations, provide accnrate geometries and electron distribution properties for drng molecnles.

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