C-Substituted Pyrrolidines from Life Chemicals Inspiring Your Drug Discovery Endeavour!

Our Unique Building Blocks to Perform Far and Wide
7 January 2020
Oleg Lukin
Senior Research Scientist

Pyrrolidines are an important class of heterocycles found in numerous natural products,1 bioactive molecules,2 organocatalysts,3 and building blocks in organic synthesis.4 There are over 60 FDA approved pyrrolidine-based drugs.5 Antihypertensive agent Captopril 1 (Figure 1) is an example of the pyrrolidine derived marketed drugs. Pyrrolidine has found its use as a core scaffold in advanced pharmaceutical research compounds and clinical candidates, e.g., Factor Xa inhibitor 2,6 NK3 receptor antagonists 3,7 and DPP-IV inhibitors 48 shown in Fig. 1. Synthesis of combinatorial libraries of functionalized pyrrolidines for HTS-based drug discovery was recently reported.9

Examples of advanced pharmaceutical compounds containing the pyrrolidine substructure

Figure 1. Examples of advanced pharmaceutical compounds containing the pyrrolidine substructure

Given the importance of the pyrrolidine substructure, Life Chemicals offers a rich structural variety of pyrrolidine-based building blocks and screening compounds for synthetic and drug discovery projects.

The full set of the title structures can be provided upon request at orders@lifechemicals.com. Please, see the representative set of available C-functionalized pyrrolidines below.

representative C-functionalized pyrrolidines available from Life Chemicals

 

References:

  1.  (a) Fukuda, Е.; Sudoh, Y.; Tsuchiya, Y.; Okuda, T.; Igarashi, Y. J. Nat. Prod.201477, 813–817. (b) Michael, J. P. Nat. Prod. Rep. 200522, 603–626. (c) Cheng, Y.; Huang, Z. T.; Wang, M. X. Curr. Org. Chem. 20048, 325–351.
  2. (a) Alvarez- Ibarra, C.; Csaky, A. G.; Lopez de Silanes, G. A.; Quiroga, M. L. J. Org. Chem. 199762, 479–484. (b) Bianco, A.; Maggini, M.; Scorrano, G.; Toniolo, C.; Marconi, G.; Villani, C.; Prato, M. J. Am. Chem. Soc. 1996118, 4072–4080.
  3.  (a) Seayad, J.; List, B. Org. Biomol. Chem. 20053, 719–724. (b) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 200443, 5138–5175.
  4. (a) Fujieda, H.; Maeda, K.; Kato, N. Org. Process Res. Dev. 201923, 69–77. (b) Campello, H. R.; Parker, J.; Perry, M.; Ryberg, P.; Gallagher, T. Org. Lett.201618, 4124–4127. (c) Notz, W.; Tanaka, F.; Barbas, C. F. Acc. Chem. Res. 200437, 580–591. (d) Felpin, F. X.; Lebreton, J. Eur. J. Org. Chem. 2003, 3693–3712. (e) Pearson, W. H. Pure Appl. Chem. 200274, 1339–1347.
  5. www.drugbank.ca; accessed in March 2019.
  6. Anselm, L.; Banner, D. W.; Benz, J.; Groebke Zbinden, K.; Himber, J.; Hilpert, H.; Huber, W.; Kuhn, B.; Mary, J.-L.; Otteneder, M. B.; Panday, N.; Ricklin, F.; Stahl, M.; Thomi, S.; Haap, W. Bioorg. Med. Chem. Lett201020, 5313–5319.
  7. Jablonski, P.; Kawasaki, K.; Knust, H.; Limberg, A.; Nettekoven, M.; Ratni, H.; Riemer, C.; Wu, X. PCT Int. Appl. O2009019163; Chem. Abstr2007147, 118261.
  8. Backes, B. J.; Longenecker, K.; Hamilton, G. L. et al. Bioorg. Med. Chem. Lett200717, 2005–2012.
  9. For combinatorial syntheses of pyrrolidine-based screening compounds, see: (a) Baumann, M.; Baxendale, I. R.; Kuratli, C.; Ley, S. V.; Martin, R. I.; Schneider. J. ACS Comb. Sci201113, 405–413. (b) Kumar, A.; Gupta, G.; Srivastava, S. J. Comb. Chem. 2010, 12, 458–462.
7 January 2020, 18:59 Oleg Lukin Building Blocks

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