Dear Colleagues,
I am starting to write a book, "Intrinsic Solubility Data for Pharmaceutical Research." I have studied 1325 publications and have compiled 6352 entries of intrinsic solubility. Still, I am sure I missed papers containing solubility-pH. If you published such, please send me a link to [email protected]. If I already have your paper, I will send you any pDISOL-X calculation results I have. I will do the same if I have missed your paper, and I will include your results in the book. Many thanks in advance,
Alex
Great News Alex. Probably you read my publication years ago:
Revisiting the solubility concept of pharmaceutical compounds
Blasko, Andrei; Leahy-Dios, Alana; Nelson, William O.; Austin, Steven A.; Killion, Robert B.; Visor, Gary C.; Massey, Ian, Monatshefte fuer Chemie (2001), 132(7), 789-798
Hi Andrei,
Nice to hear from you. Thanks for reminding me. I have a copy of your paper, which looks interesting. However, none of the compounds from your paper is in my database, probably because I could not find the structures of the molecules. In the past18 years, has Roche Biosciences made the structures public? I would like to analyze the molecules using pDISOL-X, but I need to know what the 2D structures are (SMILES or mol/sdf files will do).
Best,
Alex
I left Roche long ago. You can search using the RO number in the paper.
Dear Alex,
In 2012, I wrote a paper related to Mat- pKa tool developed to calculate pKas of molecules based on their solubility profiles.
In 2016, I used this software to determine a pKa of an enantiomer, non soluble into a aqueous solvent.
Sincerely
Lionel VIDAUD
Dear Lionel,
I read your interesting 2012 paper, but was not aware of the more recent one. Thank you. Attached is a recent publication that might be of interest to you.
Best wishes,
Alex
Dear Alex,
Impressive subject, but key subject probably for the next decade for my point of view. Many reasons for these aspects:
-Until now, high throughput technologies have needed to refer to empirical calculations of Solubility, pKas, logP and logD. These 4 parameters are essential for ADME / PK profiles, formulations of NMEs. Rules of 5 and other rules and indices (LLE, AEI, etc..) are supporting and verify each time, these 4 parameters orient the molecular profiling..
-Since 2000's, numbers and numbers of screenings have been performed, with high number of risks of over and underestimation of these 4 parameters. In these conditions, screenings have provided conclusions with high degrees of imprecision, meaning that some interesting hits would have been discarded from the selections.
-To change this way of selection, today we must become highly accurate in solubility determinations and for resolving this issue, must go to experimental data and discard empiral calculations. Consequnetly highthrough of exact solubility determinations in different acqueous buffers (eg, pH1, 3, 4.5, 6.5, 7.4, 9 ..) must be performed. From this, it would be possible to calculate experimental pKas (eg, as I suggested, or with other calculations) and then, experimental logDs would deliver experimental logPs.
-Because new subjects, beyond the rule of 5 are coming, the approach described above would take also a right and universal place.
This just my point if view, but you are certainly the best person to provide different and valuable approaches.
Best wishes
Lionel
Dear Lionel,
I completely agree with you.
Quality of measurement is very important.
I've attached another paper that might be of interest. Several logS-pH profiles there.
Best wishes,
Alex
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