Crystal structure of sorbinil, C11H9FN2O3

Kissinger, Charles R.; Adman, Elinor T.; Clark, Jim; Stenkamp, Ronald E.

doi:10.1107/s0108270185006291

Cited by 2 publications

(1 citation statement)

References 4 publications

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“…In 1978, Pfizer discovered some spirohydantoin AR inhibitors with imidazolidine-2,5-dione scaffold like Sorbinil (IC 50 = 0.5 μM) (Fig. 2) [16, 17]. Many derivatives of Sorbinil were then introduced with different halo substitution (Fig.…”

Section: Introductionmentioning

confidence: 99%

QSAR-based rational discovery of novel substituted-4′-iminospiro[indoline-3,3′-[1,2,5]thiadiazolidinyl]-2-one 1′,1′-dioxide with potent in vitro anticancer activity

et al. 2019

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Recent studies have suggested that aldose reductase inhibition preferentially inhibits the growth of cancer cells. However, the investigations of this issue are not many. Novel nine substituted- 4′-iminospiro[indoline-3,3′-[1,2,5] thiadiazolidinyl]-2-one 1′,1′-dioxide derivatives were designed by both isosteric replacement of the imidazolidine-2,5-dione moiety in spirohydantoin scaffold and conformational rigidification approaches. A QSAR with high predictive power (r 2 = 0.99) was created from a series of potent aldose reductase inhibitors and was used to predict the activity of our new compounds. Compound 5 showed the best docking score (− 33.24 kcal/mol) with the least RMSD value (< 1.5) obtained by molecular dynamic simulations over 20 ns. All compounds showed promising anticancer activities especially compound 5 that achieved the highest inhibitory activities with IC 50 ; 0.013, 0.031, 0.064, and 0.048 mmol/L against breast, colon, prostate, and lung cell lines respectively. The discovery of this lead compound confirmed the rational design. Further investigations may be required for optimization of this compound .

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Section: Introductionmentioning

confidence: 99%