N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptor

被引：13

作者：

Vallin, Karl S. A. ^{[1
]}

Sterky, Karin J. ^{[1
]}

Nyman, Eva ^{[2
]}

Bernstrom, Jenny ^{[2
,3
]}

From, Rebecka ^{[1
]}

Linde, Christian ^{[1
]}

Minidis, Alexander B. E. ^{[1
]}

Nolting, Andreas ^{[2
,3
]}

Narhi, Katja ^{[1
]}

Santangelo, Ellen M. ^{[1
]}

Sehgelmeble, Fernando W. ^{[1
]}

Sohn, Daniel ^{[1
]}

Strindlund, Jennie ^{[4
]}

Weigelt, Dirk ^{[1
]}

机构：

[1] AstraZeneca R&D, Innovat Med, Med Chem, CNSP iMed, SE-15185 Sodertalje, Sweden

[2] AstraZeneca R&D, Innovat Med, Discovery Sci, SE-15185 Sodertalje, Sweden

[3] AstraZeneca R&D, Innovat Med, Discovery Sci, SE-43183 Molndal, Sweden

[4] AstraZeneca R&D, Innovat Med, Neurosci, CNSP iMed, SE-15185 Sodertalje, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 17期

关键词：

Ion channel; TRPA1; Antagonist; ACTIVATE TRPA1; CHANNEL; DISCOVERY; A1;

D O I：

10.1016/j.bmcl.2012.07.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of potent antagonists of the ion channel transient receptor potential A1 (TRPA1) was developed by modifying lead structure 16 that was discovered by high-throughput screening. Based on lead compound 16, a SAR was established, showing a narrow region at the nitro-aromatic R-1 moiety and at the warhead, while the R-2 side had a much wider scope including ureas and carbamates. Compound 16 inhibits Ca2+-activated TRPA1 currents reversibly in whole cell patch clamp experiments, indicating that under in vivo conditions, it does not react covalently, despite its potentially electrophilic ketone. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5485 / 5492

页数：8

共 50 条

[21] TRPA1 underlies a sensing mechanism for O2
Takahashi, Nobuaki
Kuwaki, Tomoyuki
Kiyonaka, Shigeki
Numata, Tomohiro
Kozai, Daisuke
Mizuno, Yusuke
Yamamoto, Shinichiro
Naito, Shinji
Knevels, Ellen
Carmeliet, Peter
Oga, Toru
Kaneko, Shuji
Suga, Seiji
Nokami, Toshiki
Yoshida, Jun-ichi
Mori, Yasuo
NATURE CHEMICAL BIOLOGY, 2011, 7 (10) : 701 - 711
[22] TRPA1 Is a Component of the Nociceptive Response to CO2
Wang, Yuanyuan Y.
Chang, Rui B.
Liman, Emily R.
JOURNAL OF NEUROSCIENCE, 2010, 30 (39): : 12958 - 12963
[23] TRPA1 underlies a sensing mechanism for O2
Nobuaki Takahashi
Tomoyuki Kuwaki
Shigeki Kiyonaka
Tomohiro Numata
Daisuke Kozai
Yusuke Mizuno
Shinichiro Yamamoto
Shinji Naito
Ellen Knevels
Peter Carmeliet
Toru Oga
Shuji Kaneko
Seiji Suga
Toshiki Nokami
Jun-ichi Yoshida
Yasuo Mori
Nature Chemical Biology, 2011, 7 : 701 - 711
[24] Trasient receptor potential ankyrin 1 (TRPA1): a novel relevant target in Alzheimer's disease?
Bicca, M. Assuncao
Viola, K. L.
Loch-Neckel, G.
Klein, W. L.
Calixto, J. Batista
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2015, 25 : S578 - S578
[25] 2-alkyl-1-(2-aryl-1,1-difluoro-2-hydroxyethyl)benzimidazoles: potential angiotensin II receptor antagonists
Yagupolskii, LM
Fedyuk, DV
TETRAHEDRON LETTERS, 2000, 41 (13) : 2265 - 2267
[26] REACTION OF CYANAMIDE WITH ARYL(TRICHLOROMETHYL)CARBINOLS . A NOVEL SYNTHESIS OF ALKYL 5-ARYL-2-IMINO-4-OXO-1-IMIDAZOLIDINECARBOXIMIDATES
REEVE, W
BARRON, E
JOURNAL OF ORGANIC CHEMISTRY, 1969, 34 (04): : 1005 - &
[27] Species-specific pharmacology of trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists
Klionsky, Lana
Tamir, Rami
Gao, BaoXi
Wang, Weiya
Immke, David C.
Nishimura, Nobuko
Gavva, Narender R.
MOLECULAR PAIN, 2007, 3
[28] An efficient synthesis of a class of novel N-alkyl-N-aryl-4-hydroxyl-1-methyl-2-oxo-1,2-dihydro-3-quinolinecarbothioamides
Spears, GW
Tsuji, K
Tojo, T
Nishimura, H
Ogino, T
JOURNAL OF HETEROCYCLIC CHEMISTRY, 2002, 39 (04) : 799 - 804
[29] The contribution of transient receptor potential ankyrin 1 (TRPA1) to the in vivo nociceptive effects of prostaglandin E2
Dall'Acqua, Marcelo C.
Bonet, Ivan J. M.
Zampronio, Aleksander R.
Tambeli, Claudia H.
Parada, Carlos A.
Fischer, Luana
LIFE SCIENCES, 2014, 105 (1-2) : 7 - 13
[30] Direct activation of the ion channel TRPA1 by Ca2+
Zurborg, Sandra
Yurgionas, Brian
Jira, Julia A.
Caspani, Ombretta
Heppenstall, Paul A.
NATURE NEUROSCIENCE, 2007, 10 (03) : 277 - 279

← 1 2 3 4 5 →