C3-Heteroaroyl cannabinoids as photolabeling ligands for the CB2 cannabinoid receptor

被引：23

作者：

Dixon, Darryl D. ^{[1
]}

Tius, Marcus A. ^{[1
]}

Thakur, Ganesh A. ^{[2
]}

Zhou, Han ^{[2
]}

Bowman, Anna L. ^{[2
]}

Shukla, Vidyanand G. ^{[2
]}

Peng, Yan ^{[2
]}

Makriyannis, Alexandros ^{[2
]}

机构：

[1] Univ Hawaii Manoa, Dept Chem, Honolulu, HI 96822 USA

[2] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 16期

关键词：

CB2; Cannabinoid; Ligand-assisted protein structure; Photolabeling; Photoactivatable group; ADAMANTYL CANNABINOIDS; SUBSTANCE-P; ANALOGS; PROBES; REQUIREMENTS; PHARMACOLOGY; PEPTIDES; PROTEINS;

D O I：

10.1016/j.bmcl.2012.06.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tricyclic cannabinoids incorporating a heteroaroyl group at C3 were prepared as probes to explore the binding site(s) of the CB1 and CB2 receptors. This relatively unexplored structural motif is shown to be CB2 selective with K-i values at low nanomolar concentrations when the heteroaromatic group is 3-benzothiophenyl (41) or 3-indolyl (50). When photoactivated, the lead compound 41 was shown to successfully label the CB2 receptor through covalent attachment at the active site while 50 failed to label. The benzothiophenone moiety may be a photoactivatable moiety suitable for selective labeling. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5322 / 5325

页数：4

共 30 条

[1] [Anonymous], **DROPPED REF**
[2] CANNABINOIDS .3. SYNTHETIC APPROACHES TO 9-KETOCANNABINOIDS - TOTAL SYNTHESIS OF NABILONE
ARCHER, RA
BLANCHARD, WB
DAY, WA
JOHNSON, DW
LAVAGNINO, ER
RYAN, CW
BALDWIN, JE
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1977, 42 (13) : 2277 - 2284
[3] The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor
Bremer, AA
Leeman, SE
Boyd, ND
[J]. FEBS LETTERS, 2000, 486 (01) : 43 - 48
[4] Evidence for spatial proximity of two distinct receptor regions in the substance P (SP)• neurokinin-1 receptor (NK-1R) complex obtained by photolabeling the NK-1R with p-benzoylphenylalanine3-SP
Bremer, AA
Leeman, SE
Boyd, ND
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (25) : 22857 - 22861
[5] DETECTION OF CANNABINOID RECEPTORS BY PHOTOAFFINITY-LABELING
BURSTEIN, SH
AUDETTE, CA
CHARALAMBOUS, A
DOYLE, SA
GUO, Y
HUNTER, SA
MAKRIYANNIS, A
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (01) : 492 - 497
[6] CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[7] SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF ETHER AND RELATED ANALOGS OF DELTA-8-TETRAHYDROCANNABINOL, DELTA-9-TETRAHYDROCANNABINOL, AND DELTA-9,11-TETRAHYDROCANNABINOL
COMPTON, DR
PRESCOTT, WR
MARTIN, BR
SIEGEL, C
GORDON, PM
RAZDAN, RK
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (11) : 3310 - 3316
[8] Plant, synthetic, and endogenous cannabinoids in medicine
Di Marzo, V
De Petrocellis, L
[J]. ANNUAL REVIEW OF MEDICINE, 2006, 57 : 553 - 574
[9] Heteroadamantyl Cannabinoids
Dixon, Darryl D.
Sethumadhavan, Divakaramenon
Benneche, Tore
Banaag, April R.
Tius, Marcus A.
Thakur, Ganesh A.
Bowman, Anna
Wood, JodiAnne T.
Makriyannis, Alexandros
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (15) : 5656 - 5666
[10] BENZOPHENONE PHOTOPHORES IN BIOCHEMISTRY
DORMAN, G
PRESTWICH, GD
[J]. BIOCHEMISTRY, 1994, 33 (19) : 5661 - 5673

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