Novel inhibitors of fatty acid amide hydrolase

Sit, Sing‐Yuen; Conway, Charlie M.; Bertekap, Robert L.; Xie, Kai; Bourin, Clotilde; Burris, Kevin D.; Deng, Hongfeng

doi:10.1016/j.bmcl.2007.04.009

Cited by 52 publications

(49 citation statements)

References 29 publications

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“…Due the importance of FAAH as a potential target for the development of new therapeutical agents, these novel para-substituted carbamates present a useful extension to the previously reported meta-substituted carbamates as FAAH inhibitors [21][22][23][24][25], and may be useful for the development of new classes of FAAH inhibitors. Furthermore, this data may be valuable, together with that of the compounds reported earlier by us [22], in the derivation of 3D-QSAR models for the FAAH inhibition by O-phenyl carbamates.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, several FAAH inhibitors have been developed (see for review Ref. [12]), including various fatty acid derivatives [13][14][15][16][17], and non-lipid inhibitors such as a-keto heterocycles [18][19][20], carbamate derivatives [21][22][23][24][25], (thio)-hydantoins [26] and most recently, selective piperidine/piperazine ureas [27,28]. Probably, the most well-studied FAAH inhibitors are the carbamate-based 3 0 -carbamoylbiphenyl-3-yl ester (4, URB597) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors

Minkkilä

Myllymäki

Saario

et al. 2009

European Journal of Medicinal Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors

Minkkilä

Myllymäki

Saario

et al. 2009

European Journal of Medicinal Chemistry

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“…5A), which demonstrated antinociceptive effects in the formalin test and antiallodynic effects in the spinal nerve ligation model of neuropathic pain (Sit and Xie, 2002;Sit et al, 2007). ABPP analysis revealed that BMS-1 was relatively nonselective for FAAH, with multiple serine hydrolase off-targets in the brain and peripheral tissues More recently, a peripherally restricted, p-hydroxyphenyl derivative of URB597 was developed.…”

Section: A Faah Inhibitorsmentioning

confidence: 99%

Chemical Probes of Endocannabinoid Metabolism

2013

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“…FAAH-1 and FAAH-2 both hydrolyze NAEs, but have different acyl group specificities. Note that FAAH inhibitors are currently being developed as potential analgesics [35][36][37].…”

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confidence: 99%

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

Farrell

Merkler

2008

Drug Discovery Today

114

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The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. Keywords N-acylamino acid; N-acyldopamine; N-acylethanolamine; primary fatty acid amide; N-acylamideThe fatty acid amide bond has long been recognized in nature, being important in the structure of the ceramides [1] and the sphingolipids [2]. The first non-sphingosine based fatty acid amide isolated from a natural source was N-palmitoylethanolamine from egg yolk in 1957 [3]. Interest in the N-acylethanolamines (NAEs) dramatically increased upon the identification of Narachidonoylethanolamine (anandamide) as the endogenous ligand for the cannabinoid receptors in the mammalian brain [4]. It is now known that a family of NAEs is found in the brain and in other tissues [5,6].In addition to the NAEs, other classes of fatty acid amides have been characterized, namely the N-acylamino acids (NAAs) [7], the N-acyldopamines (NADAs) [8] and the primary fatty acid amides (PFAMs) [9,10] (Figure 1). Relative to NAEs, much less is currently known about the NAAs, the NADAs and the PFAMs, except that they are found in biological systems. The goal of this review is to summarize the current state of knowledge regarding the different classes of endogenous fatty acid amides and highlight their potential for drug discovery (see refs. [11-13] for earlier reviews) © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Merkler, D.J (E-mail: merkler@cas.usf.edu) phone 813-974-3579; fax 813-974-1733. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Teaser SentenceFatty acid amides are a family of mammalian bioactive compounds. These molecules and the enzymes involved in their metabolism provide an opportunity to develop new drugs to treat human disease. -palmitoyl-, N-stearoyl-and N-oleoylethanolamine [5,11], each compromising ≥25% of total brain NAEs. Other less abundant NAEs found in the brain are anandamide, N-linoleoyl-, N-linolenoyl-, N-dihomo-γ-linolenoyl-and N-docosatetraenoylethanolamine [11]. In addition to the brain, the NAEs are widespread in the peripheral tissues [5]. The mos...

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Novel inhibitors of fatty acid amide hydrolase

Cited by 52 publications

References 29 publications

The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors

The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors

Chemical Probes of Endocannabinoid Metabolism

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

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