N-(4-methoxy-7-methyl-1,3-benzothiazol-2-yl)-6-methyl-2,3-dihydro-1,4-dioxine-5-carboxamide | 1393445-58-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: N-(4-methoxy-7-methyl-1,3-benzothiazol-2-yl)-6-methyl-2,3-dihydro-1,4-dioxine-5-carboxamide
• CAS: 1393445-58-3
• 化学式: C₁₅H₁₆N₂O₄S
• 分子量: 320.369
• InChiKey: UXIBFAWMQWQKTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-甲氧基-7-甲基苯并噻唑-2-胺 、 1,4-二恶英-2-甲酰氯，5,6-二氢-3-甲基-（9CI） 生成 N-(4-methoxy-7-methyl-1,3-benzothiazol-2-yl)-6-methyl-2,3-dihydro-1,4-dioxine-5-carboxamide
  参考文献：
  名称：

  Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor

  摘要：

  Herein we describe the discovery and development of a novel class of M-4 positive allosteric modulators, culminating in the discovery of ML293. ML293 exhibited modest potency at the human M4 receptor (EC50 = 1.3 mu M) and excellent efficacy as noted by the 14.6-fold leftward shift of the agonist concentration-response curve. ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1 h, [Brain] = 10.3 mu M, B: P = 0.85). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.109