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

[41] TRPA1 Mediates Contact Hypersensitivity Induced by 2,4-Dinitrochlorobenzene
Maki-Opas, Ilari
Hamalainen, Mari
Moilanen, Lauri J.
Sood, Heini
Leppanen, Tiina
Kummola, Laura
Junitila, Ilkka S.
Letimaki, Lauri
Moilanen, Eeva
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2023, 143 (06) : 1104 - +
[42] Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain
Dai, Yi
Wang, Shenglan
Tominaga, Makoto
Yamamoto, Satoshi
Fukuoka, Tetsuo
Higashi, Tomohiro
Kobayashi, Kimiko
Obata, Koichi
Yamanaka, Hiroki
Noguchi, Koichi
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (07): : 1979 - 1987
[43] The O2-sensing TRPA1 channel regulates mitochondrial activities
Hamano, Satoshi
Takahashi, Nobuaki
Ebert, Maximilian
ReikoSakaguchi
Semba, Hiroaki
Suzuki, Jyunji
Iino, Masamitsu
Takeda, Norihiko
Mori, Yasuo
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2015, 128 (03) : S178 - S178
[44] Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels
Hasan, Raquibul
Leeson-Payne, Alasdair T. S.
Jaggar, Jonathan H.
Zhang, Xuming
SCIENTIFIC REPORTS, 2017, 7
[45] Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels
Raquibul Hasan
Alasdair T. S. Leeson-Payne
Jonathan H. Jaggar
Xuming Zhang
Scientific Reports, 7
[46] Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+
Andersson, David A.
Gentry, Clive
Moss, Sian
Bevan, Stuart
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (20) : 8374 - 8379
[47] NICKEL(2) AND COBALT(2) COMPLEXES OF PRIMARY ALKYL AMIDES[1]
CUNNINGHAM, WK
STEPHENS, RS
RAGSDALE, RO
JOURNAL OF INORGANIC & NUCLEAR CHEMISTRY, 1969, 31 (11): : 3579 - +
[48] Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1
Maftei, Daniela
Vellani, Vittorio
Artico, Marco
Giacomoni, Chiara
Severini, Cinzia
Lattanzi, Roberta
NEUROSCIENCE, 2020, 427 : 16 - 28
[49] Cubyl amides:: Novel P2X7 receptor antagonists
Gunosewoyo, Hendra
Guo, Jun Liu
Bennett, Maxwell R.
Coster, Mark J.
Kassiou, Michael
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (13) : 3720 - 3723
[50] Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents
Baraldi, Pier Giovanni
Preti, Delia
Materazzi, Serena
Geppetti, Pierangelo
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (14) : 5085 - 5107

← 1 2 3 4 5 →