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Review
. 2010 Nov 25;53(22):7902-17.
doi: 10.1021/jm100762r. Epub 2010 Aug 30.

Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore

Fraser F Fleming  1 , Lihua Yao, P C Ravikumar, Lee Funk, Brian C Shook
Affiliations
Review

Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore

Fraser F Fleming et al. J Med Chem. .
No abstract available

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Figures

Figure 1
Figure 1
Aminonitrile Vildagliptin
Figure 2
Figure 2
Nitrile-Containing Aromatase and Aldolase Inhibitors.
Figure 3
Figure 3
Non-steroidal Receptor Antagonists in which Nitriles Function as Carbonyl Bioisosteres.
Figure 4
Figure 4
Co-crystallizations in the Human Progesterone Ligand Binding Domain.
Figure 4
Figure 4
Co-crystallizations in the Human Progesterone Ligand Binding Domain.
Figure 5
Figure 5
Nitrile-Containing Farnesyltransferase Inhibitors.
Figure 6
Figure 6
Nitrile-Containing Kinase Inhibitors.
Figure 7
Figure 7
Nitrile-Substituted Cyanoquinoline as an Azomethine-Water Bioisostere.
Figure 8
Figure 8
Nitrile-Containing Cardiovascular Agents.
Figure 9
Figure 9
Nitrile-Containing CNS Drugs.
Figure 10
Figure 10
Nitrile-Containing Anti-HIV Agents.
Figure 11
Figure 11
Nitrile-Containing Xanthine Oxidase Inhibitors.
Figure 12
Figure 12
Nitrile-Containing DPP IV Inhibitors.
Figure 13
Figure 13
Miscellaneous Arylnitrile-Containing Inhibitors.
Figure 14
Figure 14
Most Widely Prescribed Nitrile-Containing Pharmaceuticals.
Figure 15
Figure 15
Bioactive Quatarnary Arylacetonitriles.
Figure 16
Figure 16
Alkenenitrile-Containing Pharmaceuticals
Figure 17
Figure 17
Cyanoguanidine Binding Motifs
Figure 18
Figure 18
N-Cyanoguanidine-Containing Drugs and Drug Leads
Figure 19
Figure 19
Amino Nitrile DPP IV Inhibitors
Figure 20
Figure 20
Cathepsin Inhibitors
Figure 21
Figure 21
Nitrile Inhibitor 76 and Progesterone (10) Overlay
Figure 22
Figure 22
Comparative Nitrile and Acid Etoposide Analogs.
Figure 21
Figure 21
Cyanoquinolines and Cyanopyridines as Azomethine-Water Bioisosteres.
Figure 22
Figure 22
ADME-Directed Evolution of Capravirine (82) into Lersivirine (33).
See this image and copyright information in PMC

References

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    1. For an example encountered during the development of Cathepsin Ka and Sb analogs see: Boyd MJ, Crane SN, Robichaud J, Scheigetz J, Black WC, Chauret N, Wang Q, Masse F, Oballa RM. Investigation of ketone warheads as alternatives to the nitrile for preparation of potent and selective cathepsin K inhibitors. Bioorg. Med. Chem. Lett. 2009;19:675–679. Patterson AW, Wood WJL, Hornsby M, Lesley S, Spraggon G, Ellman JA. Identification of Selective, Nonpeptidic Nitrile Inhibitors of Cathepsin S Using the Substrate Activity Screening Method. J. Med. Chem. 2006;49:6298–6307.

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