ω-Heteroarylalkylcarbamates as inhibitors of fatty acid amide hydrolase (FAAH)

被引：4

作者：

Terwege, Tobias ^{[1
]}

Dahlhaus, Helmut ^{[1
]}

Hanekamp, Walburga ^{[1
]}

Lehr, Matthias ^{[1
]}

机构：

[1] Univ Munster, Inst Pharmaceut & Med Chem, D-48149 Munster, Germany

来源：

MEDCHEMCOMM | 2014年 / 5卷 / 07期

关键词：

CANNABINOID RECEPTORS; DUAL INHIBITORS; SYSTEM; ENDOCANNABINOIDS; DEGRADATION; ANANDAMIDE; HYDROLYSIS; STABILITY;

D O I：

10.1039/c4md00181h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fatty acid amide hydrolase (FAAH) is a serine hydrolase that terminates the analgetic and anti-inflammatory effects of endocannabinoids such as anandamide. Herein we describe structure-activity relationship studies on a new series of omega-heteroarylalkylcarbamate inhibitors of FAAH. The most active compounds exhibit IC50 values in the low nanomolar range. Investigations on selectivity and metabolic stability of these inhibitors are also presented.

引用

页码：932 / 936

页数：5

共 30 条

[1] Enzymatic pathways that regulate endocannabinoid signaling in the nervous system [J].

Ahn, Kay ;

McKinney, Michele K. ;

Cravatt, Benjamin F. .

CHEMICAL REVIEWS, 2008, 108 (05) :1687-1707

[2] Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders [J].

Ahn, Kay ;

Johnson, Douglas S. ;

Cravatt, Benjamin F. .

EXPERT OPINION ON DRUG DISCOVERY, 2009, 4 (07) :763-784

[3] Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anandamide [J].

Boger, DL ;

Sato, H ;

Lerner, AE ;

Hedrick, MP ;

Fecik, RA ;

Miyauchi, H ;

Wilkie, GD ;

Austin, BJ ;

Patricelli, MP ;

Cravatt, BF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5044-5049

[4] NONSTEROIDAL ANTIINFLAMMATORY AGENTS .17. INHIBITION OF BOVINE CYCLOOXYGENASE AND 5-LIPOXYGENASE BY N-ALKYLDIPHENYL-PYRROLYL ACETIC AND PROPIONIC-ACID DERIVATIVES [J].

DANNHARDT, G ;

LEHR, M .

ARCHIV DER PHARMAZIE, 1993, 326 (03) :157-162

[5] Recent advances in the discovery and evaluation of fatty acid amide hydrolase inhibitors [J].

Deng, Hongfeng .

EXPERT OPINION ON DRUG DISCOVERY, 2010, 5 (10) :961-993

[6] Endocannabinoids: synthesis and degradation [J].

Di Marzo, V. .

REVIEWS OF PHYSIOLOGY, BIOCHEMISTRY AND PHARMACOLOGY, VOL 160, 2008, 160 :1-24

[7]

Fezza Filomena, 2008, V49, P101, DOI 10.1007/978-1-4020-8831-5_4

[8] 1-Indol-1-yl-propan-2-ones and related heterocyclic compounds as dual inhibitors of cytosolic phospholipase A2α and fatty acid amide hydrolase [J].

Forster, Laura ;

Ludwig, Joachim ;

Kaptur, Martina ;

Bovens, Stefanie ;

Elfringhoff, Alwine Schulze ;

Holtfrerich, Angela ;

Lehr, Matthias .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (02) :945-952

[9] High-performance liquid chromatographic assay with fluorescence detection for the evaluation of inhibitors against fatty acid amide hydrolase [J].

Forster, Laura ;

Elfringhoff, Alwine Schulze ;

Lehr, Matthias .

ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2009, 394 (06) :1679-1685

[10] The cannabinoid system and its pharmacological manipulation - a review, with emphasis upon the uptake and hydrolysis of anandamide [J].

Fowler, Christopher J. .

FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2006, 20 (06) :549-562

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