Discovery of structurally novel, potent and orally efficacious GPR119 agonists

AlperP.; AzimioaraM.; CowC.; MutnickD.; NikulinV.; MichellysP.-Y.; WangZ.; RedingE.; PaliottiM.; LiJ.; BaoD.; ZollJ.; KimY.; ZimmermanM.; GroesselT.; TuntlandT.; JosephS.B.; McNamaraP.; SeidelH.M.; EppleR.

首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Discovery of structurally novel, potent and orally efficacious GPR119 agonists

【24h】

Discovery of structurally novel, potent and orally efficacious GPR119 agonists

机译：发现结构新颖，有效和口服有效的GPR119激动剂

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Screening hit 5 was identified in a biochemical screen for GPR119 agonists. Compound 5 was structurally novel, displayed modest biochemical activity and no oral exposure, but was structurally distinct from typical GPR119 agonist scaffolds. Systematic optimization led to compound 36 with significantly improved in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse model at a dose of 10 mg/kg.

机译：在针对GPR119激动剂的生化筛选中确定了筛选结果5。化合物5在结构上是新颖的，显示适度的生化活性且没有口服暴露，但是在结构上不同于典型的GPR119激动剂支架。系统优化导致化合物36的体外活性和口服暴露显着改善，从而在体内小鼠模型中以10 mg / kg的剂量急性升高GLP1。

著录项

来源
《Bioorganic and Medicinal Chemistry Letters》 |2014年第10期|共5页
作者
AlperP.; AzimioaraM.; CowC.; MutnickD.; NikulinV.; MichellysP.-Y.; WangZ.; RedingE.; PaliottiM.; LiJ.; BaoD.; ZollJ.; KimY.; ZimmermanM.; GroesselT.; TuntlandT.; JosephS.B.; McNamaraP.; SeidelH.M.; EppleR.;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类
关键词
GPCR agonists; GPR119; Pyrazolopyrimidines; Type 2 diabetes;

机译：GPCR激动剂;GPR119;吡唑并嘧啶;2型糖尿病;

相似文献

外文文献
中文文献
专利

1. Discovery of structurally novel, potent and orally efficacious GPR119 agonists [J] . AlperP., AzimioaraM., CowC., Bioorganic and Medicinal Chemistry Letters . 2014,第10期

机译：发现结构性新颖，有效和口服有效的GPR119激动剂
2. Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H- pyrazol-3-yl] amide (SEN15924, WAY-361789) [J] . Zanaletti R., Bettinetti L., Castaldo C., Journal of Medicinal Chemistry . 2012,第10期

机译：发现一种新型的α-7烟碱乙酰胆碱受体激动剂系列，并表征有效，选择性和口服有效的激动剂5-（4-乙酰[1,4]二氮杂-1-基）戊酸[5-（4-甲氧基苯基））-1H-吡唑-3-基]酰胺（SEN15924，WAY-361789）
3. Discovery of the oxazabicyclo[3.3.1]nonane derivatives as potent and orally active GPR119 agonists [J] . Dai Xing, Stamford Andrew, Liu Hong, Bioorganic and Medicinal Chemistry Letters . 2015,第22期

机译：恶唑双环[3.3.1]壬烷衍生物作为强效和口服活性GPR119激动剂的发现
4. Discovery of Potent mMClR Agonists with Prolonged Activity at Human Melanocytes [C] . Aleksandar Todorovic, Jerry R. Holder, Rayna M. Bauzo American Peptide Symposium . 2006

机译：发现有效的MMCLR激动剂，具有延长人黑素细胞的长期活动
5. SAR studies on a weak delta opioid dipeptide antagonist (Tyr-Tic) and a potent mu opioid peptidomimetic agonist. [D] . Ma, Wenli. 2000

机译：SAR研究了一种弱δ阿片类二肽拮抗剂（Tyr-Tic）和一种有效的μ阿片类肽模拟激动剂。
6. Discovery of a Potent and Orally Efficacious TGR5Receptor Agonist [O] . Sameer Agarwal, *, Amit Patil, 2016

机译：发现有效且口服有效的TGR5受体激动剂
7. Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist [O] . Sameer Agarwal, Amit Patil, Umesh Aware, 2015

机译：发现有效和口服有效的Tgr5受体激动剂

Discovery of structurally novel, potent and orally efficacious GPR119 agonists

摘要

著录项

相似文献

相关主题

期刊订阅