- Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity
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To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.
- Taniguchi, Toru,Inagaki, Hiroaki,Baba, Daichi,Yasumatsu, Isao,Toyota, Akiko,Kaneta, Yasuyuki,Kiga, Masaki,Iimura, Shin,Odagiri, Takashi,Shibata, Yoshihiro,Ueda, Kiyono,Seo, Maki,Shimizu, Hiroki,Imaoka, Tomoki,Nakayama, Kiyoshi
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supporting information
p. 737 - 742
(2019/04/01)
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- Synthesis of pyrido and pyrazinodithienodipyrimidine-4,8(3H,9H)-dione derivatives by the aza-Wittig methodology
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A one-pot synthesis of the hitherto unreported pyrido[5″,6″:4, 5;3″2″:4′,5′]dithieno[3,2-d:3′,2′-d′] dipyrimidine-4,8(3H,9H)-dione 6a-o and pyrazino[5″,6″:4, 5;3″2″:4′,5′]dithieno[3,2-d:3′,2′-d′] dipyrimidine-4,8(3H,9H)-dione 6p-y pentaheterocyclic systems, based on the tandem aza-Wittig heterocumulene-mediated annulation strategy is described.
- Vázquez Vilarelle, David,Peinador Veira, Carlos,Quintela López, José M.
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p. 275 - 283
(2007/10/03)
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- One pot synthesis of 2,6-dichloro-3,5-dicyanopyridine from aliphatic precursors
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Malononitrile is condensed with triethyl orthoformate in the presence of pyridine; the mixture is acidified with HCl gas and after addition of further pyridine, HCl diazotised to form 2,6-dichloro-3,5-dicyanopyridine in a convenient, high yield process.
- Duindam,Lishinsky,Sikkema
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p. 2605 - 2609
(2007/10/02)
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