J. X. Qiao et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4118–4123
4123
6. (a) A torsional scan of 20-methyl-biphenyl was done at MP2/cc-PVTZ//B3LYP/
HF-631G*. Equilibrium geometries were obtained using Jaguar (Jaguar, version
6.5, Schrödinger, LLC, New York, NY, 2006), while subsequent single point
energy calculations were done using Q-Chem v3.1. A preferred twist in the
range of 40–70 degrees between the two phenyls was evident. The 90-degree
torsion present in the crystal structure incurred a small amount of strain
energy (1.1 kcal) which is likely to be near the margin of error.; (b) Jaguar, v6.5
Schrödinger, LLC, New York, NY, 2006.; (c) Shao, Y. et al Phys. Chem. Chem. Phys.
2006, 8, 3172.
biphenyl analogs. Because of the broad application of the ortho-
substituted biphenyl moieties, use of the perpendicular conforma-
tion of the alpha-substituted arylcyclopropyls to mimic the bioac-
tive conformation of ortho-substituted biaryl moieties can be
generalized and applied to achieve structural diversification and
novelty in future drug design.
7. (a) Goodman, A. L.; Eastman, R. H. J. Am. Chem. Soc. 1964, 86, 908; (b) Closs, G.
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Acknowledgments
The authors thank Dr. Chubiao Xue for insightful personal dis-
cussions and Dr. Steven Sheriff for depositing 2r-FXa complex into
PDB.
References and notes
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Opin. Drug Discov. Dev. 2004, 7, 460; (b) Walenga, J. M.; Jeske, W. P.;
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benzimidazolyl cyclopropyl P4 group with an
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