The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.

Gauthier JY; Belley M; Deschenes D; Fournier JF; Gagne S; Gareau Y; Hamel M; Henault M; Hyjazie H; Kargman S; Lavallee G; Levesque JF; Li L; Mamane Y; Mancini J; Morin N; Mulrooney E; Robichaud J; Therien M; Tranmer G; Wang Z; Wu J; Black WC

首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.

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The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.

机译：4，7-二取代的萘甲酸衍生物作为UDP竞争性P2Y14拮抗剂的鉴定。

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A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y(14) with a good pharmacokinetic profile.

机译：通过高通量筛选，鉴定出具有萘甲酸核心的嘧啶能受体P2RY（14）的弱，UDP竞争性拮抗剂。优化后的化合物具有更高的效能，但药代动力学较差。酰基葡萄糖醛酸化被确定为代谢的主要途径。增加取代基的吸电子性质显着减少了葡萄糖醛酸苷化并改善了药物动力学。进一步的优化导致鉴定出化合物38，它是具有良好药代动力学特征的P2Y（14）的8 nM UDP竞争性拮抗剂。

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《Bioorganic and Medicinal Chemistry Letters》 |2011年第10期|共4页
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Gauthier JY; Belley M; Deschenes D; Fournier JF; Gagne S; Gareau Y; Hamel M; Henault M; Hyjazie H; Kargman S; Lavallee G; Levesque JF; Li L; Mamane Y; Mancini J; Morin N; Mulrooney E; Robichaud J; Therien M; Tranmer G; Wang Z; Wu J; Black WC;
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1. The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14. [J] . Gauthier JY, Belley M, Deschenes D, Bioorganic and Medicinal Chemistry Letters . 2011,第10期

机译：4，7-二取代的萘甲酸衍生物作为UDP竞争性P2Y14拮抗剂的鉴定。
2. Synthesis and Identification of Some New 2,3-Disubstituted 1,3-Oxazepine-4,7-dione Derivatives Containing Azo Group and 1,3,4-Thiadiazole Moiety [J] . Zeid Hassan Abood, Murtadha Mohammed Hussein, Ihsan Mahdi Shaheed Asian Journal of Chemistry: An International Quarterly Research Journal of Chemistry . 2015,第8期

机译：某些新的含偶氮基和1,3,4-噻二唑部分的2,3-二取代的1,3-奥氮平-4,7-二酮衍生物的合成与鉴定
3. 1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure-activity relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives. [J] . Hall A, Brown SH, Chessell IP, Bioorganic and Medicinal Chemistry Letters . 2007,第4期

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机译：将一些2,4 - 二取代 - 苯氧基乙酸衍生物的假设设计为Crth {sub} 2受体拮抗剂：QSAR方法
5. Studies on the plant growth activity of substituted naphthoic acids [D] . Koshimizu, Koichi -1

机译：取代萘酸的植物生长活性研究
6. Exploring a 2-Naphthoic Acid Template for theStructure-Based Design of P2Y14 Receptor Antagonist MolecularProbes [O] . Evgeny Kiselev, MatthewO. Barrett, Vsevolod Katritch, -1

机译：探索2-萘甲酸模板P2Y14受体拮抗剂分子的基于结构的设计探针
7. Synthesis of 2,8-disubstituted-4,7-dioxatricyclo[3.2.1.03,6]octane and 2,6-dioxabicyclo[3.2.0]heptane derivatives starting from furan [O] . Joaquín Plumet, Ana Aljarilla 2010

机译：从呋喃开始合成2,8-二取代-4,7-二氧杂三环[3.2.1.03,6]辛烷和2,6-二氧杂双环[3.2.0]庚烷衍生物
8. Fiber Spinning from the Nematic Melt. 3. The Copolyester of p-Hydroxybenzoic Acid and 2-Hydroxy-6-naphthoic Acid [R] . Muramatsu, H., Krigbaum, W. R. 1986

机译：来自向列型熔体的纤维纺丝。 3.对羟基苯甲酸和2-羟基-6-萘甲酸的共聚酯

The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.

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