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Having introduced extent of substitution as a measure of molecular complexity in an earlier post, I was particularly interested by Dan's posts on AT7519 and AT9283. In each case, the screening hit used as a starting point for further elaboration lacked acyclic substituents.
You might wonder how you could impose this substructural requirement when selecting compounds for screening. This is actually very easy using SMARTS notation (Daylight SMARTS tutorial | OpenEye SMARTS pattern matching | SMARTS in wikipedia). The requirement that terminal non-hydrogen atoms be absent can be specified as:
D1 indicates a non-hydrogen atom (A) that is connected to only one other non-hydrogen atom and 0 requires that these cannot be present in acceptable molecules. A requirement like this can be combined with a requirement for 10 to 20 non-hydrogen atoms:
I will discuss the use of SMARTS for compound selection in more detail in connection with design of screening libraries so think of this as a taster. I've also tried to keep things simple by assuming that hydrogen atoms are implicit which means that they are treated as a property of the atoms to which they are bonded rather than as atoms in their own right.