L-798106 | 244101-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: L-798106
• 英文别名: (2E)-N-[(5-bromo-2-methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl)phenyl]-2-propenamide；(E)-N-(5-bromo-2-methoxyphenyl)sulfonyl-3-[2-(naphthalen-2-ylmethyl)phenyl]prop-2-enamide
• CAS: 244101-02-8
• 化学式: C₂₇H₂₂BrNO₄S
• 分子量: 536.446
• InChiKey: ODTKFNUPVBULRJ-NTCAYCPXSA-N

物化性质

• 密度：
  1.425±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

生物活性

L-798106 是一种强效且高度选择性的前列腺素类 EP3 受体拮抗剂（Ki=0.3 nM），在 EP4、EP1 和 EP2 受体上也表现出微摩尔活性，针对 EP4、EP1 和 EP2 的 Ki 值分别为 916 nM、大于 5000 nM 和大于 5000 nM。

靶点

Ki值：

• EP3受体：0.3 nM
• EP4受体：916 nM
• EP1/2受体：＞5000 nM

反应信息

• 作为产物：
  描述：

  methyl (E)-3-(2’-(bromomethyl)phenyl)acrylate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 四(三苯基膦)钯 、 cesium fluoride 、 N,N'-1,2-ethylenediylbis-(L-cysteine) diethyl ester dihydrochloride 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 1,2-二氯乙烷 、 叔丁醇 为溶剂， 反应 14.0h， 生成 L-798106
  参考文献：
  名称：

  Structure–activity relationship of cinnamic acylsulfonamide analogues on the human EP3 prostanoid receptor

  摘要：

  Potent and selective antagonists of the human EP3 receptor have been identified. The structure-activity relationship of the chemical series was conducted and we found several analogues displaying sub-nanomolar K-i values at the EP3 receptor and micromolar activities at the EP1, EP2 and EP4 receptors. The effect of added human serum albumin (HSA) on the binding affinity at the EP3 receptor was also investigated. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00110-9

文献信息

• REMEDIES FOR PRURITUS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1426059A1

  公开（公告）日：2004-06-09

  The present invention relates to agents for treating and/or preventing pruritus which comprise, as the active ingredient, the compound with antagonistic activity for EP3 receptor which is one of prostaglandin E2 receptor subtypes. The compounds with antagonistic activity for EP3 are useful in treating and/or preventing pruritus in diseases with itch, example for, eczema, urticaria, contact dermatitis, atopic dermatitis, dermatitis herpetiformis, psoriasis, lichen planus, rhus dermatitis, biliary obstruction, uremia, lymphoma, leukemia, polycythemia vera, dry skin, or hemodialysis performed in treating renal involvement with chronic glomerulonephritis, diabetes mellitus, nephrosclerosis, cystic kidney or systemic disease, or conjunctivitis.

  本发明涉及治疗和/或预防瘙痒症的制剂，其活性成分包括对前列腺素E2受体亚型之一的EP3受体具有拮抗活性的化合物。具有 EP3 拮抗活性的化合物可用于治疗和/或预防瘙痒性疾病中的瘙痒，例如湿疹、荨麻疹、接触性皮炎、特应性皮炎、疱疹性皮炎、银屑病、扁平苔藓、疹性皮炎、胆道梗阻、尿毒症、胆道梗阻、尿毒症、淋巴瘤、白血病、真性红细胞增多症、皮肤干燥症，或为治疗慢性肾小球肾炎、糖尿病、肾硬化症、囊性肾或全身性疾病或结膜炎等肾脏病而进行的血液透析。
• Neurofibromatoses therapeutic agents and screening for same
  申请人：Fernandez-Valle Cristina

  公开号：US10105351B2

  公开（公告）日：2018-10-23

  Disclosed herein are methods of treating a patient at risk of developing or having a neurofibromatosis or a sporadic schwannoma. In exemplary embodiments, the method involves administering to a subject in need an effective amount of a modulator of a target related to neurofibromatosis. Also disclosed are screening assays involving the implementation of Merlin-null Schwann cells, and to compounds identified using same.

  本文公开了治疗有患神经纤维瘤病或散发性分裂瘤风险的患者的方法。在示例性实施方案中，该方法涉及向有需要的受试者施用有效量的神经纤维瘤病相关靶点的调节剂。还公开了涉及实施Merlin-null许旺细胞的筛选试验，以及利用这些试验鉴定的化合物。
• Remedies for pruritus
  申请人：——

  公开号：US20040235955A1

  公开（公告）日：2004-11-25

  The present invention relates to agents for treating and/or preventing pruritus which comprise, as the active ingredient, the compound with antagonistic activity for EP 3 receptor which is one of prostaglandin E 2 receptor subtypes. The compounds with antagonistic activity for EP 3 are useful in treating and/or preventing pruritus in diseases with itch, example for, eczema, urticaria, contact dermatitis, atopic dermatitis, dermatitis herpetiformis, psoriasis, lichen planus, rhus dermatitis, biliary obstruction, uremia, lymphoma, leukemia, polycythemia vera, dry skin, or hemodialysis performed in treating renal involvement with chronic glomerulonephritis, diabetes mellitus, nephrosclerosis, cystic kidney or systemic disease, or conjunctivitis.

  本发明涉及治疗和/或预防瘙痒症的制剂，其活性成分包括对 EP 3 受体具有拮抗活性的化合物，该受体是前列腺素 E 2 受体亚型之一。具有拮抗 EP 3 可用于治疗和/或预防瘙痒性疾病中的瘙痒，例如湿疹、荨麻疹、接触性皮炎、特应性皮炎、疱疹性皮炎、银屑病、扁平苔藓、疹性皮炎、胆道梗阻、尿毒症、淋巴瘤、白血病、真性红细胞增多症、皮肤干燥症等、尿毒症、淋巴瘤、白血病、真性红细胞增多症、皮肤干燥症，或为治疗慢性肾小球肾 炎、糖尿病、肾硬化症、囊性肾或全身性疾病或结膜炎等肾脏疾病而进行的血液透析。
• NEUROFIBROMATOSES THERAPEUTIC AGENTS AND SCREENING FOR SAME
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：EP2825209A1

  公开（公告）日：2015-01-21
• Genes Associated With Type ll Diabetes Mellitus
  申请人：Chissoe Stephanie

  公开号：US20080200568A1

  公开（公告）日：2008-08-21

  Genes associated with Type II Diabetes Mellitus (T2DM) are identified and screening methods to identify chemical compounds that act on those targets for the treatment of T2DM or its associated pathologies are discussed. The use of EP3 antagonist was found to affect blood glucose levels in mice fed a high-fat diet and made insulin deficient by streptozocin injection.