Structure-Based Design and Synthesis of Potent, Ethylenediamine-Based, Mammalian Farnesyltransferase Inhibitors as Anticancer Agents was written by Fletcher, Steven;Keaney, Erin Pusateri;Cummings, Christopher G.;Blaskovich, Michelle A.;Hast, Michael A.;Glenn, Matthew P.;Chang, Sung-Youn;Bucher, Cynthia J.;Floyd, Ryan J.;Katt, William P.;Gelb, Michael H.;Van Voorhis, Wesley C.;Beese, Lorena S.;Sebti, Said M.;Hamilton, Andrew D.. And the article was included in Journal of Medicinal Chemistry in 2010.Formula: C6H3FN2 This article mentions the following:
A potent class of anticancer, human farnesyltransferase (hFTase) inhibitors has been identified by “piggy-backing” on potent, antimalarial inhibitors of Plasmodium falciparum farnesyltransferase (PfFTase). On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating the extensive structure-activity relationship (SAR) study reported herein. The most potent inhibitor is compound I, which exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Moreover, it is noteworthy that several of the inhibitors proved highly selective for hFTase (up to 333-fold) over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of inhibitor II co-crystallized with farnesyl pyrophosphate (FPP) in the active site of rat FTase illustrates that the para-benzonitrile moiety of II is stabilized by a π-π stacking interaction with the Y361β residue, suggesting a structural explanation for the observed importance of this component of our inhibitors. In the experiment, the researchers used many compounds, for example, 6-Fluoronicotinonitrile (cas: 3939-12-6Formula: C6H3FN2).
6-Fluoronicotinonitrile (cas: 3939-12-6) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Formula: C6H3FN2