tag:blogger.com,1999:blog-1136153439451224584.post8815141387018556792..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Just Because its called "Fragment-Based"...Dr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger4125tag:blogger.com,1999:blog-1136153439451224584.post-21782472656904352602015-06-01T12:44:53.633-07:002015-06-01T12:44:53.633-07:00Gee, back in the day, we would just call this &quo...Gee, back in the day, we would just call this "medicinal chemistry". And pretty rudimentary medicinal chemistry, at that. Like, sophomore-in-college-medicinal-chemistry. Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-21524654914873681082015-05-24T07:50:38.139-07:002015-05-24T07:50:38.139-07:00Another pretty shitty aspect of this paper is that...Another pretty shitty aspect of this paper is that 2,4-diaminopyrimidines with a small substituent in 5 position are so promiscuos that when explored in combichem fashion (for which they are ideal since the 4 subsitution is much faster than 2 substitution) they are 100% guaranteed to provide high potency kinase inhibitor, for any kinase that you wish. They obvious difficulty is that there is almost no selectivity against unrelated classes of kinases. So if one start from bis-aminosubstituted pyrimidine hit, there needs to be some serious X-ray based optimization work.milkshakehttps://www.blogger.com/profile/08188961610554710616noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-92131920613417947992015-05-21T20:44:29.296-07:002015-05-21T20:44:29.296-07:00On the other hand, having been in this field for a...On the other hand, having been in this field for as long as I have, it is kind of nice to see fragments used as a selling point, rather than something hidden away in the basement and discussed only in whispers.<br /><br />That said, the word "novel" comes up 10 times in the text of the article, and another 4 times in the references - seems like novelty is quite common!Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-24140498152232226832015-05-21T08:34:34.222-07:002015-05-21T08:34:34.222-07:00I can't see the article (and don't feel es...I can't see the article (and don't feel especially deprived by this) and this seems to be a hybridization approach which people have been doing for years. Probably more accurate to describe the design as 'modular' than 'fragment-based' because relevant groups are not assayed (or even docked) as fragments. When doing this sort of thing one should be particularly alert to the possibility of non-additivity in the SAR. Peter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.com