17414-73-2Relevant academic research and scientific papers
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
Design, synthesis, and anti-HCV activity of thiourea compounds
Kang, Iou-Jiun,Wang, Li-Wen,Lee, Chung-Chi,Lee, Yen-Chun,Chao, Yu-Sheng,Hsu, Tsu-An,Chern, Jyh-Haur
scheme or table, p. 1950 - 1955 (2009/11/30)
A series of thiourea derivatives were synthesized and their antiviral activity was evaluated in a cell-based HCV subgenomic replicon assay. SAR studies revealed that the chain length and the position of the alkyl linker largely influenced the in vitro anti-HCV activity of this class of potent antiviral agents. Among this series of compounds synthesized, the thiourea derivative with a six-carbon alkyl linker at the meta-position of the central phenyl ring (10) was identified as the most potent anti-HCV inhibitor (EC50 = 0.047 μM) with a selectivity index of 596.
N,N-dimethylglycine-promoted ullmann-type coupling reactions of aryl iodides with aliphatic alcohols
Zhang, Hui,Ma, Dawei,Cao, Weiguo
, p. 243 - 246 (2007/10/03)
The Ullmann-type coupling reactions of aryl iodides and aliphatic alcohols occur at 110°C with N,N-dimethylglycine as the ligand, giving aryl alkyl ethers in good to excellent yields. Georg Thieme Verlag Stuttgart.
Non-peptidic cyclophilin binding compounds and their use
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, (2008/06/13)
The invention relates to non-peptidic compounds that possess bioactive properties, such as the ability to protect neuronal cells from otherwise lethal treatments or the ability to promote the growth or regeneration of neuronal cells. In part, the inventio
Non-peptidic cyclophilin binding compounds and their use
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Page 11, (2010/02/06)
The invention relates to non-peptidic compounds that possess bioactive properties, such as the ability to protect neuronal cells from otherwise lethal treatments or the ability to promote the growth or regeneration of neuronal cells. In part, the inventio
Non-peptidic cyclophilin binding compounds and their use
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, (2008/06/13)
This invention relates to pharmaceutical compositions and methods of using non-peptidic cyclophilin-binding compounds in medical conditions involving breakdown of mitochondrial energy metabolism induced by calcium overload, in treating alopecia and promot
