7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid chloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid chloride
• 英文别名: 7-Methoxy-2-oxo-8-pentyloxy-1,2-dihydro-quinoline-3-carbonyl chloride；7-methoxy-2-oxo-8-pentoxy-1H-quinoline-3-carbonyl chloride
• 化学式: C₁₆H₁₈ClNO₄
• 分子量: 323.776
• InChiKey: ADDOERFXEIDPML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid chloride 在 ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.5h， 以85%的产率得到7-methoxy-2-oxo-8-(pentyloxy)-1,2-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  Synthesis and SAR Studies of 2-Oxoquinoline Derivatives as CB2 Receptor Inverse Agonists

  摘要：

  The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.

  DOI：

  10.1021/jm050879z
• 作为产物：
  描述：

  7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 在 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid chloride
  参考文献：
  名称：

  Synthesis and SAR Studies of 2-Oxoquinoline Derivatives as CB2 Receptor Inverse Agonists

  摘要：

  The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.

  DOI：

  10.1021/jm050879z

文献信息

• Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging
  作者：Mingzhang Gao、Min Wang、Kathy D. Miller、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1016/j.bmc.2010.02.011

  日期：2010.3

  family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled 2-oxoquinoline and 2-chloroquinoline derivatives, [11C]6a–d and [11C]9a–d, were prepared by O-[11C]methylation

  最近有人提出将大麻素作为潜在的抗肿瘤药物的新家族，并且认为大麻素受体2（CB2）在肿瘤细胞中过表达。这项研究旨在利用生物医学成像技术正电子发射断层扫描（PET）开发用于癌症中CB2受体成像的新型放射性配体。碳11标记的2-氧喹啉和2-氯喹啉衍生物[ 11 C] 6a - d和[ 11 C] 9a - d是通过使用[ 11 C] CH对相应的前体进行O- [ 11 C]甲基化制备的3OTf在基本条件下并通过简化的固相萃取（SPE）方法进行分离，以[ 11 C] CO 2为基础，以40％至50％的放射化学收率进行了分离，并将衰变校正为轰击结束（EOB）。EOB的总合成时间为15–20分钟，放射化学纯度> 99％，合成结束时的比活（EOS）为111–185 GBq /μmol。放射性配体结合试验表明，化合物6f，6b和9f表现出强大的体外结合亲和力，纳摩尔摩尔K i值，对CB2的选择性至少100-2000倍。
• Cannabinoid receptor inverse agonists and neutral antagonists as therapeutic agents for the treatment of bone disorders
  申请人：Ralston Hamilton Stuart

  公开号：US20060172019A1

  公开（公告）日：2006-08-03

  The present invention pertains to cannabinoid (CB) receptor inverse agonists and neutral antagonists, and especially CB1 and CB2 inverse agonists and neutral antagonists; such as, for example, certain pyrazole compounds; their use in the inhibition of osteoclasts (for example, the inhibition of the survival, formation, and/or activity of osteoclasts), and/or in the inhibition of bone resorption; their use in connection with treatment of bone disorders, such as conditions mediated by osteoclasts (e.g., increased osteoclast activity) and/or characterised by (e.g., increased) bone resorption, such as osteoporosis (e.g., osteoporosis not associated with inflammation; e.g., osteoporosis associated with a genetic predisposition, sex hormone deficiency, or ageing), cancer associated bone disease, and Paget's disease of bone.

  本发明涉及大麻素（CB）受体的反向激动剂和中性拮抗剂，尤其是CB1和CB2的反向激动剂和中性拮抗剂，例如某些吡唑化合物；它们用于抑制破骨细胞（例如抑制破骨细胞的存活、形成和/或活动），和/或抑制骨吸收；它们用于治疗骨疾病，例如由破骨细胞介导的疾病（例如破骨细胞活性增加）和/或以（例如增加的）骨吸收为特征的疾病，例如骨质疏松症（例如与炎症无关的骨质疏松症；例如与遗传倾向、性激素缺乏或衰老有关的骨质疏松症）、癌症相关骨疾病和Paget骨病。
• CANNABINOID RECEPTOR INVERSE AGONISTS AND NEUTRAL ANTAGONISTS AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE DISORDERS
  申请人：The University Court of The University of Aberdeen

  公开号：EP1606019A1

  公开（公告）日：2005-12-21
• [EN] CANNABINOID RECEPTOR INVERSE AGONISTS AND NEUTRAL ANTAGONISTS AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE DISORDERS<br/>[FR] AGONISTES INVERSES DE RECEPTEURS DE CANNABINOIDES ET ANTAGONISTES NEUTRES AGISSANT EN TANT QU'AGENTS THERAPEUTIQUES DESTINES AU TRAITEMENT DE TROUBLES OSSEUX
  申请人：UNIV ABERDEEN

  公开号：WO2004078261A1

  公开（公告）日：2004-09-16

  The present invention pertains to cannabinoid (CB) receptor inverse agonists and neutral antagonists, and especially CB1 and CB2 inverse agonists and neutral antagonists; such as, for example, certain pyrazole compounds; their use in the inhibition of osteoclasts (for example, the inhibition of the survival, formation, and/or activity of osteoclasts), and/or in the inhibition of bone resorption; their use in connection with treatment of bone disorders, such as conditions mediated by osteoclasts (e.g., increased osteoclast activity) and/or characterised by (e.g., increased) bone resorption, such as osteoporosis (e.g., osteoporosis not associated with inflammation; e.g., osteoporosis associated with a genetic predisposition, sex hormone deficiency, or ageing), cancer associated bone disease, and Paget's disease of bone.
• Synthesis and SAR Studies of 2-Oxoquinoline Derivatives as CB2 Receptor Inverse Agonists
  作者：Katri H. Raitio、Juha R. Savinainen、Jouko Vepsäläinen、Jarmo T. Laitinen、Antti Poso、Tomi Järvinen、Tapio Nevalainen

  DOI：10.1021/jm050879z

  日期：2006.3.1

  The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.