Small molecule drug innovation from the molecular skeleton.

CA is the most comprehensive database of small molecules and peptide chemical structures, so if analytical chemical structures do have first-hand materials, the relationship between chemical structures and innovation is complex.
authors have pointed out some of the problems they have analyzed, such as molecular shape changes that are not necessarily more innovative than side chain changes.
and benzene rings are classic electron isometrics (i.e. biological functions are more likely to be consistent), but one is a pentatony ring and one is a six-ring, so according to the definition of this article belongs to different pioneer.
the link between the two ring structures is also a skeleton change, but it doesn't always lead to significant functional changes.
and side chain changes may sometimes lead to greater active changes than these two types of skeleton changes, such as changes from hydrophobic side chains to polar side chains.
of course, such large-scale analysis is unlikely to have a perfect standard definition, and these observations do reflect, to some extent, some of the changes in the development of small molecule drugs.
the demand for molecular skeletons is driven by two things, one target nature and one patent pressure.
the genome, the speed of target discovery increased rapidly, and worth a try was everywhere.
different natural substrates of different family proteins, so the requirements for small molecular complexes are also different.
Although because the evolution of convenient proteins is composed of a small number of protein domain arrangements, some so-called dominant skeletons can be combined with a variety of proteins, but the active binding cavity of different family proteins is generally still very different.
this is why it is difficult to screen new protein families such as phosphatase and histogenesin methyl transferase liens.
is another factor forcing manufacturers to look for new skeletons, because any new skeleton patent application will circle the surrounding ten miles and eight villages.
the patent department's demands on Markush have improved, the average tracker tries to avoid patent lawsuits with unpredictable consequences and structurally try to stay away.
one of the reasons why there aren't many of these new skeletons.
of course these two drivers are not enough, before manufacturers also want to escape other people's patents, but not technically allowed.
The development of synthetic technology, the commercial supply of complex intermediates, and the maturity of computer-aided drug design have greatly improved the design and implementation capabilities of molecular skeletons, and the evaluation of high-volume bioactive activity has made large-scale testing possible.
Even though active similars to new skeletons are rare, because chemists can quickly synthesize many of them, biologists can quickly evaluate these compounds, so looking for needles in a haystack can identify a few high-quality compounds.
such as DEL can synthesize billions of compounds without moving, and many of the similars are new skeletons as defined in this article, so millions of skeletons are just a small target.
it is unrealistic to look for new molecular skeletons on such a large scale in an age when chemical structure identification can take months and activity can only be evaluated with whole animals.
of course, strictly speaking, many so-called new skeleton and side chain modification ratio is only fifty steps, the real active new molecular skeleton is still very difficult to find.
patients do not care much about the molecular skeleton old and new, the key is to see the efficacy and benefits.
new bottle is a good thing, but whether the wine inside is different is the most important.
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