To design molecule, I care about not only biological activity but also molecular properties.
Because if chemist do molecular design only focused on biological activity, it will produce many problems.
I read short letter of J. Med. Chem. lett. ASAP article.
The letter shows some interesting data.
I often use LE, LLE but not used PFI before.
GSK uses PFI (property forecast indices) to asses the probability of development risk.
PFI is calculated by sum of Chrom LogD + HAr rings. And They shows probability of risk as traffic light colors. I like the analyse.
And there are some papers that analysed the impact of aromatic ring on compound developability.
LogP, Num of aromatic rings is good indices because it’s easy to understand and big impact for drug likeness.
So, I think PFI is interesting parameter.
And I think the traffic light colors Green(go!), Yellow(careful), Red(Stop) is very easy to understand I like it.
Another interesting data, They summarised mean of vitro activity and property changes in optimizations reported in major medchem papers in table1.
The author shows there was significant difference in LLE between two groups. One group assessed lipophilic influence in design. And another group did not.
If the data is true, I want to know the origin of Yes group is pharmaceutical companies or academia or both.
I often fall in a dilemma, need more activity but increase lipophilicity to increase activity, it maybe not good for another properties.
Am I not good medicinal chemist ?
There are a lot of method to design molecule i.e. SBDD, FBDD, CADD, or HTS etc. I have to use these tools and organise data and design molecule more efficiently.
Need study more and more…