Synthesis and Evaluation of 1H-Pyrrolo[2,3-b]pyridine Derivatives as Novel Immunomodulators Targeting Janus Kinase 3
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- Nakajima Yutaka
- Drug Discovery Research, Astellas Pharma Inc.
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- Tojo Takashi
- Drug Discovery Research, Astellas Pharma Inc.
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- Morita Masataka
- Drug Discovery Research, Astellas Pharma Inc.
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- Hatanaka Keiko
- Drug Discovery Research, Astellas Pharma Inc.
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- Shirakami Shohei
- Drug Discovery Research, Astellas Pharma Inc.
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- Tanaka Akira
- Drug Discovery Research, Astellas Pharma Inc.
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- Sasaki Hiroshi
- Drug Discovery Research, Astellas Pharma Inc.
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- Nakai Kazuo
- Drug Discovery Research, Astellas Pharma Inc.
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- Mukoyoshi Koichiro
- Drug Discovery Research, Astellas Pharma Inc.
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- Hamaguchi Hisao
- Drug Discovery Research, Astellas Pharma Inc.
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- Takahashi Fumie
- Drug Discovery Research, Astellas Pharma Inc.
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- Moritomo Ayako
- Drug Discovery Research, Astellas Pharma Inc.
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- Higashi Yasuyuki
- Drug Discovery Research, Astellas Pharma Inc.
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- Inoue Takayuki
- Drug Discovery Research, Astellas Pharma Inc.
書誌事項
- タイトル別名
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- Synthesis and Evaluation of 1<i>H</i>-Pyrrolo[2,3-<i>b</i>]pyridine Derivatives as Novel Immunomodulators Targeting Janus Kinase 3
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抄録
Janus kinases (JAKs) have been known to play crucial roles in modulating a number of inflammatory and immune mediators. Here, we describe a series of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting JAK3 for use in treating immune diseases such as organ transplantation. In the chemical modification of compound 6, the introduction of a carbamoyl group to the C5-position and substitution of a cyclohexylamino group at the C4-position of the 1H-pyrrolo[2,3-b]pyridine ring led to a large increase in JAK3 inhibitory activity. Compound 14c was identified as a potent, moderately selective JAK3 inhibitor, and the immunomodulating effect of 14c on interleukin-2-stimulated T cell proliferation was shown. Docking calculations and WaterMap analysis of the 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives were conducted to confirm the substituent effects on JAK3 inhibitory activity.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 63 (5), 341-353, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204176610944
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- NII論文ID
- 130005067249
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 026355183
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- PubMed
- 25786493
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可