Figure 2.11 Representative examples of (a) multifunctional spiro building blocks and (b) lead compounds for screening that are currently available from commercial vendors.
References
1 1 Moss, G. (1999). Extension and revision of the nomenclature for spiro compounds. Pure Appl. Chem. 71 (3): 531–558.
2 2 Knox, C., Law, V., Jewison, T. et al. (2011). DrugBank 3.0: a comprehensive resource for “omics” research on drugs. Nucleic Acids Res. 39: D1035–D1041.
3 3 Krebs, A., Schafer, B., and Kochner, A. (2010). Method for producing azoniaspironortropine esters and nortropan‐3‐one compounds, US2010048903.
4 4 Smith, L.K. and Baxendale, I.R. (2015). Total syntheses of natural products containing spirocarbocycles. Org. Biomol. Chem. 13 (39): 9907–9933.
5 5 Zhang, F.‐M., Zhang, S.‐Y., and Tu, Y.‐Q. (2018). Recent progress in the isolation, bioactivity, biosynthesis, and total synthesis of natural spiroketals. Nat. Prod. Rep. 35 (1): 75–104.
6 6 Perron, F. and Albizati, K.F. (1989). Chemistry of spiroketals. Chem. Rev. 89 (7): 1617–1661.
7 7 Quintavalla, A. (2018). Spirolactones: recent advances in natural products, bioactive compounds and synthetic strategies. Curr. Med. Chem. 25 (8): 917–962.
8 8 Anthoni, U., Chevolot, L., Larsen, C. et al. (1987). Marine alkaloids. 12. chartellines, halogenated beta‐lactam alkaloids from the marine bryozoan Chartella papyracea. J. Org. Chem. 52 (21): 4709–4712.
9 9 Manam, R.R., Teisan, S., White, D.J. et al. (2005). Lajollamycin, a nitro‐tetraene spiro‐β‐lactone‐γ‐lactam antibiotic from the marine actinomycete Streptomyces nodosus. J. Nat. Prod. 68 (2): 240–243.
10 10 Arulananda Babu, S., Padmavathi, R., Ahmad Aslam, N., and Rajkumar, V. (2015). Chapter 8 ‐ recent developments on the synthesis and applications of natural products‐inspired spirooxindole frameworks. In: Studies in Natural Products Chemistry, vol. 46 (ed. R. Attaur), 227–339. Elsevier.
11 11 Hong, L. and Wang, R. (2013). Recent advances in asymmetric organocatalytic construction of 3,3′‐spirocyclic oxindoles. Adv. Synth. Catal. 355 (6): 1023–1052.
12 12 Singh, G.S. and Desta, Z.Y. (2012). Isatins as privileged molecules in design and synthesis of spiro‐fused cyclic frameworks. Chem. Rev. 112 (11): 6104–6155.
13 13 Wang, J., Soisson, S.M., Young, K. et al. (2006). Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 441 (7091): 358–361.
14 14 Häbich, D. and von Nussbaum, F. (2006). Platensimycin, a new antibiotic and “superbug challenger” from nature. ChemMedChem 1 (9): 951–954.
15 15 Nicolaou, K.C., Li, A., and Edmonds, D.J. (2006). Total synthesis of platensimycin. Angew. Chem. Int. Ed. 45 (42): 7086–7090.
16 16 Trost, B.M., Surivet, J.‐P., and Toste, F.D. (2004). Ruthenium‐catalyzed enyne cycloisomerizations. Effect of allylic silyl ether on regioselectivity. J. Am. Chem. Soc. 126 (47): 15592–15602.
17 17 Nicolaou, K.C., Li, A., Edmonds, D.J. et al. (2009). Total synthesis of platensimycin and related natural products. J. Am. Chem. Soc. 131 (46): 16905–16918.
18 18 Trajkovic, M., Ferjancic, Z., Saicic, R.N., and Bihelovic, F. (2019). Enantioselective synthesis of the platensimycin core by silver(I)‐promoted cyclization of Δ6‐α‐iodoketone. Chem. Eur. J. 25 (17): 4340–4344.
19 19 Ghosh, A.K. and Xi, K. (2007). Enantioselective synthesis of (−)‐platensimycin oxatetracyclic core by using an intramolecular Diels−Alder reaction. Org. Lett. 9 (20): 4013–4016.
20 20 Taylor, F.F. and Faloon, W.W. (1959). The role of potassium in the natriuretic response to a steroidal lactone (SC‐9420). J. Clin. Endocrinol. Metab. 19 (12): 1683–1687.
21 21 Roughley, S.D. and Jordan, A.M. (2011). The medicinal chemist’s toolbox: an analysis of reactions used in the pursuit of drug candidates. J. Med. Chem. 54 (10): 3451–3479.
22 22 Clemons, P.A., Bodycombe, N.E., Carrinski, H.A. et al. (2010). Small molecules of different origins have distinct distributions of structural complexity that correlate with protein‐binding profiles. Proc. Natl. Acad. Sci. U. S. A. 107 (44): 18787–18792.
23 23 Brooks, W.H., Guida, W.C., and Daniel, K.G. (2011). The significance of chirality in drug design and development. Curr. Top. Med. Chem. 11 (7): 760–770.
24 24 Nguyen, L.A., He, H., and Pham‐Huy, C. (2006). Chiral drugs: an overview. Int. J. Biomed. Sci. 2 (2): 85–100.
25 25 Matthews, S.J. and McCoy, C. (2003). Thalidomide: a review of approved and investigational uses. Clin. Ther. 25 (2): 342–395.
26 26 Lovering, F., Bikker, J., and Humblet, C. (2009). Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52 (21): 6752–6756.
27 27 Lovering, F. (2013). Escape from flatland 2: complexity and promiscuity. Med. Chem. Commun. 4 (3): 515–519.
28 28 Wipf, P., Skoda, E.M., and Mann, A. (2015). Chapter 11 – conformational restriction and steric hindrance in medicinal chemistry. In: The Practice of Medicinal Chemistry, 4e (eds. C.G. Wermuth, D. Aldous, P. Raboisson and D. Rognan), 279–299. San Diego: Academic Press.
29 29 Leeson, P.D. and Springthorpe, B. (2007). The influence of drug‐like concepts on decision‐making in medicinal chemistry. Nat. Rev. Drug Discov. 6 (11): 881.
30 30 Aldeghi, M., Malhotra, S., Selwood, D.L., and Chan, A.W.E. (2014). Two‐ and three‐dimensional rings in drugs. Chem. Biol. Drug Des. 83 (4): 450–461.
31 31 Ritchie, T.J. and Macdonald, S.J.F. (2009). The impact of aromatic ring count on compound developability – are too many aromatic rings a liability in drug design? Drug Discov. Today 14 (21): 1011–1020.
32 32 Zheng, Y.‐J. and Tice, C.M. (2016). The utilization of spirocyclic scaffolds in novel drug discovery. Expert Opin. Drug Discov. 11 (9): 831–834.
33 33 Zheng, Y., Tice, C.M., and Singh, S.B. (2014). The use of spirocyclic scaffolds in drug discovery. Bioorg. Med. Chem. Lett. 24 (16): 3673–3682.
34 34 Zhao, Y., Aguilar, A., Bernard, D., and Wang, S. (2015). Small‐molecule inhibitors of the MDM2‐p53 protein‐protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment. J. Med. Chem. 58 (3): 1038–1052.
35 35 Skalniak, L., Surmiak, E., and Holak, T.A. (2019). A therapeutic patent overview of MDM2/X‐targeted therapies (2014–2018). Expert Opin. Ther. Pat. 29 (3): 151–170.
36 36 de Jonge, M., de Weger, V.A., Dickson, M.A. et al. (2017). A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours. Eur. J. Cancer 76: 144–151.
37 37 de Weger, V.A., de Jonge, M., Langenberg, M.H.G. et al. (2019). A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours. Br. J. Cancer 120 (3): 286–293.
38 38 Brown, Z.Z., Akula, K., Arzumanyan, A. et al. (2012). A spiroligomer α‐helix mimic that binds HDM2, penetrates human cells and stabilizes HDM2 in cell culture. PLoS One 7 (10): e45948.
39 39 Brown, Z.Z. and Schafmeister, C.E. (2010). Synthesis of hexa‐ and pentasubstituted diketopiperazines from sterically hindered amino acids. Org. Lett. 12 (7): 1436–1439.
40 40 Schafmeister, C.E., Brown, Z.Z., and Gupta, S. (2008). Shape‐programmable macromolecules. Acc. Chem. Res. 41 (10): 1387–1398.
41 41 MK‐1602 Clinical trials. https://clinicaltrials.gov/ct2/results?term=MK‐1602&age_v=&gndr=&type=&rslt=&phase=2&Search=Apply