Fragment-Based Drug Discovery: Difference between revisions

| scope="col" width="5000px" | Compound 2 has high affinity for Bcl-xl but has an even higher affinity for HSA. For this reason, when HSA is present, compound 2 and similar ligands are more likely to bind to HSA thereby decreasing the amount that can bind with Bcl-xl. In order to decrease the affinity for HSA while maintaining affinity for Bcl-xl, SAR by NMR was used to compare compound 2 with a <scene name='Sandbox_reserved_394/Compound_3/1'>thioethylamino-2,4-dimethylphenyl analogue</scene>, which also has high affinity for HSA. It was found that <scene name='Sandbox_reserved_394/Compound_3/2'>two hydrophobic portions</scene> of compound 2 had very strong hydrophobic interactions with HSA. Therefore, these portions were modified with polar substituents to decrease HSA affinity. To decrease hydrophobicity, the fluorobiphenyl system was substituted with a <scene name='Sandbox_reserved_394/Piperazine_ring/1'>piperazine ring</scene> and a 2-dimethylaminoethyl group was added to the thioethylamino linkage group.