Aldrich ChemFiles 2007, 7.8, 9.

The (R)-2-methylpyrrolidinyl fragment has been a common structural motif present in several recently reported inhibitors and antagonists. One group synthesized a series of HIV-1 reverse transcriptase inhibitors of which the structure derived from (R)-2-methylpyrrolidine (Figure 1) displayed the greatest degree of inhibition.1 Another group used (R)-2-methylpyrrolidine as a key building block for a series of histamine H3 receptor antagonists which display subnanomolar potency (Scheme 1).2

Figure 1

Scheme 1 (679097)

N-Boc-4-oxo-L-proline has recently been employed as a building block in the synthesis of a chimeric S-proline-methionine residue (Scheme 2).3 This residue was incorporated into a series of N-formyl tripeptide analogues which were analyzed for their activity as agonists or antagonists of formylpeptide receptors.

Scheme 2 (681202)

1-Benzyl-3-aminopyrrolidine was used to create a series of potent dopamine D4 antagonists that are selective over D2 and a1 receptors (Scheme 3).4 These antagonists show promise in the treatment of various disorders such as ADHD, Parkinson’s disease and sexual dysfunction.

Scheme 3 (675814)

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  1. Krajewski, K. et al. Bioorg. Med. Chem. Lett. 2006, 16, 3034.
  2. Sun, M. et al. J. Med. Chem. 2005, 48, 6482.
  3. Mollica, A. et al. Bioorg. Med. Chem. 2006, 14, 2253.
  4. Egle, I. et al. Bioorg. Med. Chem. Lett. 2004, 14, 4847.

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