(+)JQ-1 has been studied both as a potential anti-cancer drug and male birth control. It functions as a bromodomain inhibitor seen in the study of selective inhibition of BET bromodomains by Filippakopoulos, et al. This work presents results of DFT (B3LYP) calculations of geometries and electrostatic potentials of (+)JQ-1 and its synthetic precursors. Similar calculations were performed to conduct conformational analyses on several structural precursors to (+)-JQ1, including (I) 1H-1,4-diazepin-2(3H)-imine, (II) 9H-[1,2,4]triazolo[4,3-a][1,4]diazepine, (III) 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine, and (IV) 4-(4-chlorophenyl)-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine; studies are reported on monobrominated species (I)-(IV) substituted at the chiral center of the seven member ring, including a comparison of the energetics of equatorial versus axial bromination of each precursor. Implications with regard to structure of (+)-JQ1 are discussed.

Chemical characteristics of precursors to (+)-JQ1: A computational study

247th National Meeting (2014)

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