67449-23-4Relevant articles and documents
Quinazolin-4-one derivatives from Streptomyces isolates
Maskey, Rajendra P.,Shaaban, Mohamed,Gruen-Wollny, Iris,Laatsch, Hartmut
, p. 1131 - 1134 (2004)
From the ethyl acetate extract of the strain Streptomyces sp. isolate GW23/1540, besides 16 known products, several 1H-quinazolin-4-one derivatives were isolated. (S*R*)-2-(1-Hydroxyethyl)-2-methyl-2,3-dihydro-1H- quinazolin-4-one (4) and (R*R*)-2-(1-hydr
Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer
Shirai, Fumiyuki,Mizutani, Anna,Yashiroda, Yoko,Tsumura, Takeshi,Kano, Yuko,Muramatsu, Yukiko,Chikada, Tsubasa,Yuki, Hitomi,Niwa, Hideaki,Sato, Shin,Washizuka, Kenichi,Koda, Yasuko,Mazaki, Yui,Jang, Myung-Kyu,Yoshida, Haruka,Nagamori, Akiko,Okue, Masayuki,Watanabe, Takashi,Kitamura, Kouichi,Shitara, Eiki,Honma, Teruki,Umehara, Takashi,Shirouzu, Mikako,Fukami, Takehiro,Seimiya, Hiroyuki,Yoshida, Minoru,Koyama, Hiroo
supporting information, p. 4183 - 4204 (2020/05/20)
Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase inhibitor. Herein we describe the optimization process of RK-287107 leading to RK-582, which exhibits a markedly improved robust tumor growth inhibition in a COLO-320DM mouse xenograft model when orally administered. In addition to the dose-dependent elevation and attenuation of the levels of biomarkers AXIN2 and β-catenin, respectively, results of the TCF reporter and cell proliferation studies on COLO-320DM are discussed.
Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles
Holmes, Jane L.,Almeida, Lynsie,Barlaam, Bernard,Croft, Rosemary A.,Dishington, Allan P.,Gingipalli, Laksmaiah,Hassall, Lorraine A.,Hawkins, Janet L.,Ioannidis, Stephanos,Johannes, Jeffrey W.,McGuire, Thomas M.,Moore, Jane E.,Patel, Anil,Pike, Kurt G.,Pontz, Timothy,Wu, Xiaoyun,Wang, Tao,Zhang, Hai-Jun,Zheng, Xiaolan
supporting information, p. 1226 - 1234 (2016/05/19)
Examples of hydroxymethylated analogues of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones are sparse or non-existent in the scientific literature. We have demonstrated that such compounds are accessible by using standard procedures from readily available raw materials.