The Discovery of 4-{1-({2,5-Dimethyl-4-4-(trifluoromethyl)benzyl-3-thienyl}carbonyl)am inocyclopropyl}benzoic Acid (MK-2894), A Potent and Selective Prostaglandin E-2 Subtype 4 Receptor Antagonist

Blouin M; Han YX; Burch JFarand JMellon CGaudreault MWrona MLevesque JFDenis DMathieu MCStocco RVigneault ETherien AClark PRowland SXu DGONeill GDucharme YFriesen R

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The Discovery of 4-{1-({2,5-Dimethyl-4-4-(trifluoromethyl)benzyl-3-thienyl}carbonyl)am inocyclopropyl}benzoic Acid (MK-2894), A Potent and Selective Prostaglandin E-2 Subtype 4 Receptor Antagonist

机译：4-{1-（{2,5-二甲基-4-4-（三氟甲基）苄基-3-噻吩基}羰基）胺基环丙基}苯甲酸（MK-2894）的发现，这是一种有效的选择性前列腺素E-2亚型4受体拮抗剂

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The discovery of highly potent and selective second generation EP4 antagonist MK-2894 (34d) is discussed. This compound exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of pain/inflammation. It also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.

机译：讨论了高效和选择性的第二代EP4拮抗剂MK-2894（34d）的发现。该化合物在许多临床前物种中表现出良好的药代动力学特征，并在几种疼痛/炎症动物模型中具有有效的抗炎活性。与传统的非甾体抗炎药吲哚美辛相比，它还在大鼠中显示出良好的胃肠道耐受性。

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来源
《Journal of Medicinal Chemistry》 |2010年第5期|2227-2238|共12页
作者
Blouin M; Han YX; Burch JFarand JMellon CGaudreault MWrona MLevesque JFDenis DMathieu MCStocco RVigneault ETherien AClark PRowland SXu DGONeill GDucharme YFriesen R;
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作者单位

Merck Frosst Canada Ltd, Merck Frosst Ctr Therapeut Res, Dept Med Chem, Kirkland, PQ H9H 3L1, Canada.;

Merck Frosst Canada Ltd, Merck Frosst Ctr Therapeut Res, Dept DMPK, Kirkland, PQ H9H 3L1, Canada.;

Merck Frosst Canada Ltd, Merck Frosst Ctr Therapeut Res, Dept In Vitro Sci, Kirkland, PQ H9H 3L1, Canada.Merck Frosst Canada Ltd, Merck Frosst Ctr Therapeut Res, Dept In Vivo Sci, Kirkland, PQ H9H 3L1, Canada.;

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正文语种英语
中图分类药学;
关键词
EP4 RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; RHEUMATOID-ARTHRITIS; CARDIOVASCULAR RISK; JOINT INFLAMMATION; COX-2 INHIBITORS; CELL-GROWTH; CYCLOOXYGENASE-2; PAIN; PROSTACYCLIN;

机译：EP4受体;药理学表征;类风湿性关节炎;心血管风险;关节发炎;COX-2 抑制剂;细胞生长;环氧合酶-2;疼痛;前列环素;

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The Discovery of 4-{1-({2,5-Dimethyl-4-4-(trifluoromethyl)benzyl-3-thienyl}carbonyl)am inocyclopropyl}benzoic Acid (MK-2894), A Potent and Selective Prostaglandin E-2 Subtype 4 Receptor Antagonist

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