1357473-72-3Relevant academic research and scientific papers
INHIBITORS OF RHO ASSOCIATED PROTEIN KINASES (ROCK) AND METHODS OF USE
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, (2013/08/15)
Compounds and compositions having activity as inhibitors of Rho-associated proteinkinases (ROCKs), and methods of making and using the subject compounds are disclosed.
Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors
Li, Rongshi,Martin, Mathew P.,Liu, Yan,Wang, Binglin,Patel, Ronil A.,Zhu, Jin-Yi,Sun, Nan,Pireddu, Roberta,Lawrence, Nicholas J.,Li, Jiannong,Haura, Eric B.,Sung, Shen-Shu,Guida, Wayne C.,Schonbrunn, Ernst,Sebti, Said M.
, p. 2474 - 2478 (2012/05/20)
Using high concentration biochemical assays and fragment-based screening assisted by structure-guided design, we discovered a novel class of Rho-kinase inhibitors. Compound 18 was equipotent for ROCK1 (IC50 = 650 nM) and ROCK2 (IC50 = 670 nM), whereas compound 24 was more selective for ROCK2 (IC50 = 100 nM) over ROCK1 (IC50 = 1690 nM). The crystal structure of the compound 18-ROCK1 complex revealed that 18 is a type 1 inhibitor that binds the hinge region in the ATP binding site. Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells.
Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists
Sakamoto, Toshihiro,Moriya, Minoru,Haga, Yuji,Takahashi, Toshiyuki,Shibata, Takunobu,Okamoto, Osamu,Nonoshita, Katsumasa,Kitazawa, Hidefumi,Hidaka, Masayasu,Gomori, Akira,Iwaasa, Hisashi,Ishihara, Akane,Kanatani, Akio,Fukami, Takehiro,Gao, Ying-Duo,MacNeil, Douglas J.,Yang, Lihu
scheme or table, p. 1564 - 1568 (2009/12/07)
A series of spiroindoline-3,4′-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats
Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds
Sakamoto, Toshihiro,Moriya, Minoru,Tsuge, Hiroyasu,Takahashi, Toshiyuki,Haga, Yuji,Nonoshita, Katsumasa,Okamoto, Osamu,Takahashi, Hirobumi,Sakuraba, Aya,Hirohashi, Tomoko,Shibata, Takunobu,Kanno, Tetsuya,Ito, Junko,Iwaasa, Hisashi,Gomori, Akira,Ishihara, Akane,Fukuroda, Takahiro,Kanatani, Akio,Fukami, Takehiro
experimental part, p. 5015 - 5026 (2009/12/04)
Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure-activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic
