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Review
. 2011 Aug 15;21(16):4674-85.
doi: 10.1016/j.bmcl.2011.06.096. Epub 2011 Jun 28.

The discovery and development of inhibitors of fatty acid amide hydrolase (FAAH)

Katerina Otrubova  1 , Cyrine Ezzili, Dale L Boger
Affiliations
Review

The discovery and development of inhibitors of fatty acid amide hydrolase (FAAH)

Katerina Otrubova et al. Bioorg Med Chem Lett. .

Abstract

A summary of the discovery and advancement of inhibitors of fatty acid amide hydrolase (FAAH) is presented.

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Figures

Figure 1
Figure 1
2-Octyl α-bromoacetoacetate and a more potent synthetic analogue.
Figure 2
Figure 2
Representative early inhibitors of FAAH.
Figure 3
Figure 3
Representative trifluoromethyl ketone inhibitors.
Figure 4
Figure 4
Representative initial α-ketoheterocycle inhibitors.
Figure 5
Figure 5
Characteristic modifications in the fatty acid side chain.
Figure 6
Figure 6
Representative C5 substituted α-ketooxazoles and structure of OL-135.
Figure 7
Figure 7
Plot of–Log Ki versus σp.
Figure 8
Figure 8
Representative exploration of the C2 acyl side chain.
Figure 9
Figure 9
Key variations of the central activating heterocycle.
Figure 10
Figure 10
Representative further conformational constraints in the C2 acyl side chain.
Figure 11
Figure 11
Additional classes of reversible FAAH inhibitors.
Figure 12
Figure 12
Recent classes of reversible FAAH inhibitors.
Figure 13
Figure 13
Additional reversible FAAH inhibitors.
Figure 14
Figure 14
β-Lactam FAAH inhibitors.
Figure 15
Figure 15
O-Aryl carbamates.
Figure 16
Figure 16
Representative carbamate hybrids.
Figure 17
Figure 17
Additional early carbamates.
Figure 18
Figure 18
Subsequent carbamate inhibitors.
Figure 19
Figure 19
Oxazole ketone/carbamate inhibitors.
Figure 20
Figure 20
Representative piperazine carbamates.
Figure 21
Figure 21
Tetrazole-based inhibitors.
Figure 22
Figure 22
Additional triazolopyridine and azole FAAH inhibitors.
Figure 23
Figure 23
Piperazine aryl urea inhibitors.
Figure 24
Figure 24
Piperidine/piperazine urea-based inhibitors of FAAH.
Figure 25
Figure 25
Additional urea inhibitors.
Figure 26
Figure 26
Tetrasubstituted urea inhibitor.
Scheme 1
Scheme 1
Carbamylation of active site Serine 241.
Scheme 2
Scheme 2
Carbamylation of active site Serine 241.
Scheme 3
Scheme 3
Activating conformational change of urea group.
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