182949-79-7Relevant articles and documents
6-Cyclohexylmethyl-3-hydroxypyrimidine-2,4-dione as an inhibitor scaffold of HIV reverase transcriptase: Impacts of the 3-OH on inhibiting RNase H and polymerase
Tang, Jing,Kirby, Karen A.,Huber, Andrew D.,Casey, Mary C.,Ji, Juan,Wilson, Daniel J.,Sarafianos, Stefan G.,Wang, Zhengqiang
, p. 168 - 179 (2017/02/15)
3-Hydroxypyrimidine-2,4-dione (HPD) represents a versatile chemical core in the design of inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H and integrase strand transfer (INST). We report herein the design, synthesis and biological evaluation of an HPD subtype (4) featuring a cyclohexylmethyl group at the C-6 position. Antiviral testing showed that most analogues of 4 inhibited HIV-1 in the low nanomolar to submicromolar range, without cytotoxicity at concentrations up to 100?μM. Biochemically, these analogues dually inhibited both the polymerase (pol) and the RNase H functions of RT, but not INST. Co-crystal structure of 4a with RT revealed a nonnucleoside RT inhibitor (NNRTI) binding mode. Interestingly, chemotype 11, the synthetic precursor of 4 lacking the 3-OH group, did not inhibit RNase H while potently inhibiting pol. By virtue of the potent antiviral activity and biochemical RNase H inhibition, HPD subtype 4 could provide a viable platform for eventually achieving potent and selective RNase H inhibition through further medicinal chemistry.
New substituted isochromans
Unterhalt,Joestingmeier
, p. 641 - 644 (2007/10/03)
Isochromans with substituents in the aromatic ring are described. They are synthesised by cyclisation of related chloromethyl-2-phenylethyl ethers. The activated 1-position of the isochromans is essential for obtaining potential drugs.
