Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design was written by Good, Andrew C.;Liu, Jinyu;Hirth, Bradford;Asmussen, Gary;Xiang, Yibin;Biemann, Hans-Peter;Bishop, Kimberly A.;Fremgen, Trisha;Fitzgerald, Maria;Gladysheva, Tatiana;Jain, Annuradha;Jancsics, Katherine;Metz, Markus;Papoulis, Andrew;Skerlj, Renato;Stepp, J. David;Wei, Ronnie R.. And the article was included in Journal of Medicinal Chemistry in 2012.Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione This article mentions the following:
We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallog. and docking data analyses have been undertaken using inhibitor complexes derived from an inhouse surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallog. observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone. In the experiment, the researchers used many compounds, for example, 6-Bromoquinoxaline-2,3(1H,4H)-dione (cas: 1910-90-3Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione).
6-Bromoquinoxaline-2,3(1H,4H)-dione (cas: 1910-90-3) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione
Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider