Structural Optimization of Ghrelin Receptor Inverse Agonists to Improve Lipophilicity and Avoid Mechanism-Based CYP3A4 Inactivation
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- Takahashi Bitoku
- Asubio Pharma Co., Ltd.
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- Funami Hideaki
- Asubio Pharma Co., Ltd.
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- Shibata Makoto
- Asubio Pharma Co., Ltd.
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- Maruoka Hiroshi
- Asubio Pharma Co., Ltd.
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- Koyama Makoto
- Asubio Pharma Co., Ltd.
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- Kanki Satomi
- Asubio Pharma Co., Ltd.
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- Muto Tsuyoshi
- Asubio Pharma Co., Ltd.
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Abstract
Structural optimization of 2-aminonicotinamide derivatives as ghrelin receptor inverse agonists is reported. So as to avoid mechanism-based inactivation (MBI) of CYP3A4, 1,3-benzodioxol ring of the lead compound was modified. Improvement of the main activity and lipophilicity was achieved simultaneously, leading to compound 18a, which showed high lipophilic ligand efficiency (LLE) and low MBI activity.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 63 (10), 825-832, 2015
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390001204178833792
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- NII Article ID
- 130005100927
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 026764369
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- PubMed
- 26423040
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed
