tag:blogger.com,1999:blog-1136153439451224584.post8666601706819519361..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: To grow or to link: why not both?Dr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-1136153439451224584.post-35850738463805844842009-11-03T18:01:08.856-08:002009-11-03T18:01:08.856-08:00There is a very nice paper from Astex (J. Med. Che...There is a very nice paper from Astex (J. Med. Chem. 2006, 49, 1346-1355) that reaches basically the same conclusions. It investigates fragment linking in Thrombin inhibition. Although their linked compound is about 10000 fold more potent than the single fragments, they say that conformation of the 2 fragments change once linked, resulting in the loss of important H-bond interactions. Thus, potency is driven only by lipophilicity. They conclude that even if the compound is not a suitable candidate for development, it is still a valuable starting point for lead optimisation.Claudio Dnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-66502934562766255032009-10-29T05:32:55.421-07:002009-10-29T05:32:55.421-07:00Oh and the link to the article didn't work for...Oh and the link to the article didn't work for me.<br />Here: http://www.ncbi.nlm.nih.gov/pubmed/19780086Bastardhttps://www.blogger.com/profile/04773584479244051660noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-87559588287189307112009-10-29T05:30:50.586-07:002009-10-29T05:30:50.586-07:00More importantly the linker is a result of fragmen...More importantly the linker is a result of fragment growing.<br />But it's a nice article.Bastardhttps://www.blogger.com/profile/04773584479244051660noreply@blogger.com