Heteroarylureas with fused bicyclic diamine cores as inhibitors of fatty acid amide hydrolase

被引：4

作者：

Keith, John M. ^{[1
]}

Jones, William ^{[1
]}

Pierce, Joan M. ^{[1
,2
]}

Seierstad, Mark ^{[1
]}

Palmer, James A. ^{[1
]}

Webb, Michael ^{[1
,3
]}

Karbarz, Mark ^{[1
,4
]}

Scott, Brian P. ^{[1
]}

Wilson, Sandy J. ^{[1
,5
]}

Luo, Lin ^{[1
,6
]}

Wennerholm, Michelle ^{[1
]}

Chang, Leon ^{[1
]}

Rizzolio, Michele ^{[1
]}

Rynberg, Raymond ^{[1
]}

Chaplan, Sandra ^{[1
]}

Breitenbucher, J. Guy ^{[1
,7
]}

机构：

[1] Janssen Pharmaceut Co Johnson & Johnson LLC, 3210 Merryfield Row, San Diego, CA 92121 USA

[2] 6405 Cedar Waters Dr, Raleigh, NC 27607 USA

[3] Mitobridge, 1030 Massachusetts Ave, Cambridge, MA 02138 USA

[4] Portola Pharmaceut, 270 East Grand Ave, San Francisco, CA 94080 USA

[5] 15 Ceder Hill Ln S, Moriarty, NM 87035 USA

[6] Vertex Pharmaceut, 3215 Merryfield Row, San Diego, CA 92121 USA

[7] 2433 North Summit Cir Glen, Escondido, CA 92026 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 20期

关键词：

FAAH; Inhibitors; Endocannabinoid; Covalent inhibitor; Anandamide; Serine hydrolase; Enzyme; Aryl urea; ALPHA-KETOHETEROCYCLE INHIBITORS; POTENT; ENZYME; FAAH; ANANDAMIDE; MARIJUANA; CANNABINOIDS; DERIVATIVES; MECHANISM; DISCOVERY;

D O I：

10.1016/j.bmcl.2020.127463

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Several compounds equipotent against both species were identified and profiled in vivo.

引用

页数：5

共 49 条

[1]

Abouab-Dellah A., 2004, [No title captured], Patent No. [2004099176, WO 2004/099176]

[2] Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity [J].

Ahn, Kyunghye ;

Johnson, Douglas S. ;

Fitzgerald, Laura R. ;

Liimatta, Marya ;

Arendse, Andrea ;

Stevenson, Tracy ;

Lund, Eric. T. ;

Nugent, Richard A. ;

Nomanbhoy, Tyzoon K. ;

Alexander, Jessica P. ;

Cravatt, Benjamin F. .

BIOCHEMISTRY, 2007, 46 (45) :13019-13030

[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] Discovery of a potent, selective, and efficacious class of reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics [J].

Boger, DL ;

Miyauchi, H ;

Du, W ;

Hardouin, C ;

Fecik, RA ;

Cheng, H ;

Hwang, I ;

Hedrick, MP ;

Leung, D ;

Acevedo, O ;

Guimaraes, CRW ;

Jorgensen, WL ;

Cravatt, BF .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :1849-1856

[5] Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides [J].

Cravatt, BF ;

Giang, DK ;

Mayfield, SP ;

Boger, DL ;

Lerner, RA ;

Gilula, NB .

NATURE, 1996, 384 (6604) :83-87

[6] Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase [J].

Cravatt, BF ;

Demarest, K ;

Patricelli, MP ;

Bracey, MH ;

Giang, DK ;

Martin, BR ;

Lichtman, AH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9371-9376

[7] ISOLATION AND STRUCTURE OF A BRAIN CONSTITUENT THAT BINDS TO THE CANNABINOID RECEPTOR [J].

DEVANE, WA ;

HANUS, L ;

BREUER, A ;

PERTWEE, RG ;

STEVENSON, LA ;

GRIFFIN, G ;

GIBSON, D ;

MANDELBAUM, A ;

ETINGER, A ;

MECHOULAM, R .

SCIENCE, 1992, 258 (5090) :1946-1949

[8] α-Ketoheterocycle inhibitors of fatty acid amide hydrolase: Exploration of conformational constraints in the acyl side chain [J].

Duncan, Katharine K. ;

Otrubova, Katerina ;

Boger, Dale L. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (09) :2763-2770

[9] Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597):: Effects on anandamide and oleoylethanolamide deactivation [J].

Fegley, D ;

Gaetani, S ;

Duranti, A ;

Tontini, A ;

Mor, M ;

Tarzia, G ;

Piomelli, D .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (01) :352-358

[10] Elucidation of fatty acid amide hydrolase inhibition by potent α-ketoheterocycle derivatives from Monte Carlo simulations [J].

Guimaraes, CRW ;

Boger, DL ;

Jorgensen, WL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (49) :17377-17384

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