6-(3-氯-1-氧代丙基)-2(3h)-苯噁唑酮 | 132383-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 中文名称: 6-(3-氯-1-氧代丙基)-2(3h)-苯噁唑酮
• 中文别名: 6-(3-氯丙醇基)苯并[D]恶唑-2(3H)-酮
• 英文名称: 6-(3-chloropropanoyl)-2,3-dihydro-1,3-benzoxazol-2-one
• 英文别名: 6-(3-chloropropanoyl)benzo[d]oxazol-2(3H)-one；6-(3-chloropropionyl)-3H-benzoxazol-2-one；6-(3-chloropropionyl)benzoxazolin-2-one；3-chloro-1-(2,3-dihydro-2-oxobenzoxazol-6-yl)-1-propanone；6-(3-chloropropionyl)benzoxazolinone；6-(3-chloropropanoyl)-3H-1,3-benzoxazol-2-one
• CAS: 132383-36-9
• 化学式: C₁₀H₈ClNO₃
• 分子量: 225.631
• InChiKey: MXIZTDFUEUBMPE-UHFFFAOYSA-N

物化性质

• 熔点：
  166 °C(Solv: ethanol (64-17-5))
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  6-(3-氯-1-氧代丙基)-2(3h)-苯噁唑酮 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 1-(4-amino-3-hydroxy-phenyl)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-1-one
  参考文献：
  名称：

  Radiosynthesis and pharmacological evaluation of [11C]EMD-95885: a high affinity ligand for NR2B-containing NMDA receptors

  摘要：

  EMD-95885, 6-[3-[4-(4-fluorobenzyl)piperidino]propionyl]-3H-benzoxazol-2-one (1) has been described as a selective antagonist for the NMDA receptors containing NR2B subunits, displaying an IC50 of 3.9 nM for this subtype. EMD-95885 (1) has been synthesized in good overall yield and labelled with carbon-11 (T-1/2: 20.4min) at its benzoxazolinone moiety using [C-11]phosgene. The pharmacological profile of [C-11]EMD-95885 ([C-11]-1) was evaluated in vivo in rats with biodistribution studies and brain radioactivity monitored with intracerebral radiosensitive (beta-microprobes. The brain uptake of [C-11]-1 was homogeneous (0.4-0.6% ID/mL) across the different brain structures studied. This in vivo brain regional distribution of [C-11]-1 was not consistent with the known distribution of NR2B subunits. Also as a measure of specificity the hippocampus/cerebellum ratio reached 0.8 throughout the time course of the experiment supporting the lack of specificity. Competition studies with the NR2B prototypic ligand ifenprodil and EMD-95885 (1), 30 min before the radioligand injection, displayed homogeneous reduction of [(11) C]-1 uptake of 40-60%. Pre-treatment of rats with DTG (sigma ligand), MDL105519 (glycine site antagonist) and MK801 (ion channel blocker) had no inhibitory effect on [C-11]-1 uptake. Use of haloperidol as a blocking drug also resulted in a homogeneous inhibition of [C-11]-1 uptake by 66-60%, which does not reflect binding to dopamine or a receptors. Due to the homogeneous radioligand uptake and inhibition and no measure of cerebral blood flow effects during these blocking studies it is uncertain whether any specific binding is observed. In view of these results, [C-11]EMD-95885 ([C-11]-1) does not have the required properties for imaging NR2B containing NMDA receptors using positron emission tomography. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.065
• 作为产物：
  描述：

  2-苯并唑啉酮 、 3-氯丙酰氯 在 aluminum (III) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以73%的产率得到6-(3-氯-1-氧代丙基)-2(3h)-苯噁唑酮
  参考文献：
  名称：

  BI-2545的发现：一种新型的自分泌抑制素抑制剂，可显着降低体内LPA水平

  摘要：

  为了寻找新的治疗干预措施来解决特发性肺纤维化患者未满足的医疗需求，我们启动了一项程序，以识别新的自分泌运动因子（ATX）抑制剂。从最近发表的化合物（PF-8380）开始，我们鉴定了几种具有改善的药代动力学和安全性的高效ATX抑制剂。进一步的优化工作导致鉴定出一位数的纳米摩尔铅化合物（BI-2545），该化合物在体内LPA显着降低，因此被认为是进行进一步研究的有价值的工具。

  DOI：

  10.1021/acsmedchemlett.7b00312

文献信息

• 2-OXO-3-BENZYLBENZOXAZOL-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS MET KINASE INHIBITORS FOR THE TREATMENT OF TUMOURS
  申请人：Schadt Oliver

  公开号：US20100280030A1

  公开（公告）日：2010-11-04

  Compounds of the formula (I), in which R 1 , R 2 , R 3 , R 3′ , R 4 , R 4′ , E, E′, E″ and E′″ have the meanings indicated in Claim 1 , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.

  式（I）中的化合物，其中R1，R2，R3，R3'，R4，R4'，E，E'，E"和E'"的含义如权利要求书中所示，是酪氨酸激酶的抑制剂，特别是Met激酶的抑制剂，并可用于治疗肿瘤。
• Heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06319916B1

  公开（公告）日：2001-11-20

  A compound of the formula: wherein ring A is an optionally substituted benzene ring; ring B′ is an optionally substituted non-aromatic heterocyclic ring having, the same or different, two or more hetero atoms; R1 is a hydrogen atom or an optionally substituted hydrocarbon group, which may be different from one another in the repetition of n; Y is an optionally substituted amino group or an optionally substituted N-containing saturated heterocyclic group; n denotes an integer of 1 to 10, provided that when the ring B′ is a 5- to 7-membered ring, the ring B′ contains at least one nitrogen atom as hetero atom and n denotes an integer of 2 to 10, or a salt thereof. The compounds and salts thereof have an excellent cholinesterase inhibitory activity and antidepressant activity, and are useful as therapeutic and/or prophylactic medicaments of senile dementia.

  该化合物的结构式如下：其中环A是一个可选择取代的苯环；环B'是一个可选择取代的非芳香杂环，具有相同或不同的两个或两个以上的杂原子；R1是一个氢原子或一个可选择取代的烃基，它们在n的重复中可能不同；Y是一个可选择取代的氨基或一个可选择取代的含氮饱和杂环基团；n表示1到10的整数，条件是当环B'是一个5-至7-成员环时，环B'至少包含一个氮原子作为杂原子，n表示2到10的整数，或其盐。该化合物及其盐具有出色的胆碱酯酶抑制活性和抗抑郁活性，并可用作老年性痴呆症的治疗和/或预防药物。
• HETEROCYCLIC COMPOUNDS AS AUTOTAXIN INHIBITORS
  申请人：Staehle Wolfgang

  公开号：US20120015959A1

  公开（公告）日：2012-01-19

  Compounds of the formula (I), in which Het, R, X, Y, R 1 and p have the meanings indicated in claim 1 , are autotaxin inhibitors and can be employed for the treatment of tumours.

  式（I）中的化合物，其中Het、R、X、Y、R1和p具有权利要求1中所示的含义，是自动税酯酶抑制剂，可用于治疗肿瘤。
• A Novel Autotaxin Inhibitor Reduces Lysophosphatidic Acid Levels in Plasma and the Site of Inflammation
  作者：James Gierse、Atli Thorarensen、Konstantine Beltey、Erica Bradshaw-Pierce、Luz Cortes-Burgos、Troii Hall、Amy Johnston、Michael Murphy、Olga Nemirovskiy、Shinji Ogawa、Lyle Pegg、Matthew Pelc、Michael Prinsen、Mark Schnute、Jay Wendling、Steve Wene、Robin Weinberg、Arthur Wittwer、Ben Zweifel、Jaime Masferrer

  DOI：10.1124/jpet.110.165845

  日期：2010.7

  Autotaxin is the enzyme responsible for the production of lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC), and it is up-regulated in many inflammatory conditions, including but not limited to cancer, arthritis, and multiple sclerosis. LPA signaling causes angiogenesis, mitosis, cell proliferation, and cytokine secretion. Inhibition of autotaxin may have anti-inflammatory properties in a variety of diseases; however, this hypothesis has not been tested pharmacologically because of the lack of potent inhibitors. Here, we report the development of a potent autotaxin inhibitor, PF-8380 [6-(3-(piperazin-1-yl)propanoyl)benzo[d]oxazol-2(3 H )-one] with an IC50 of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of autotaxin inhibition. Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380, dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen. Inhibition of plasma autotaxin activity correlated with inhibition of autotaxin at the site of inflammation and in ex vivo whole blood. Furthermore, a close pharmacokinetic/pharmacodynamic relationship was observed, which suggests that LPA is rapidly formed and degraded in vivo. PF-8380 can serve as a tool compound for elucidating LPA's role in inflammation.

  自体交联蛋白是一种负责从溶血磷脂酰胆碱（LPC）中产生溶血磷脂酸（LPA）的酶，它在许多炎症中都会上调，包括但不限于癌症、关节炎和多发性硬化症。LPA 信号传导会导致血管生成、有丝分裂、细胞增殖和细胞因子分泌。抑制自体交感神经可能对多种疾病具有抗炎作用；然而，由于缺乏有效的抑制剂，这一假设尚未得到药理测试。在此，我们报告了一种强效自体表皮生长因子抑制剂 PF-8380 [6-(3-(哌嗪-1-基)丙酰基)苯并[d]恶唑-2(3 H )-one] 的研发情况，该抑制剂在离体酶测定中的 IC50 值为 2.8 nM，在人体全血中的 IC50 值为 101 nM。PF-8380 具有足够的口服生物利用度和体内测试自体表皮生长因子抑制作用所需的暴露量。在大鼠气囊模型中测试了自体交联素在血浆和炎症部位产生 LPA 的作用。口服 30 毫克/千克的特异性抑制剂 PF-8380 可在 3 小时内使血浆和气囊中的 LPA 减少 95%以上，这表明自体表皮生长因子是炎症期间 LPA 的主要来源。每公斤 30 毫克的 PF-8380 与每公斤 30 毫克的萘普生具有相同的降低炎症性痛觉的功效。血浆自体表皮生长因子活性的抑制与炎症部位和体外全血中自体表皮生长因子的抑制相关。此外，还观察到一种密切的药代动力学/药效学关系，这表明 LPA 在体内迅速形成和降解。PF-8380 可作为一种工具化合物，用于阐明 LPA 在炎症中的作用。
• 4,4-Diphenylpiperidine Compounds or Pharmaceutically Acceptable Salts Thereof, Pharmaceutical Compositions and Uses Thereof
  申请人：Academy of Military Medical Sciences

  公开号：US20190359604A1

  公开（公告）日：2019-11-28

  The invention belongs to the field of medicine and chemical industry and relates to a 4,4-diphenylpiperidine compound or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same and uses thereof. In particular, the invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, and to a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof. In the present invention, the compound or pharmaceutically acceptable salt thereof and the pharmaceutical composition have significant activity in blocking an N-type calcium channel, and have good pharmacokinetic properties, can effectively relieve pain, and have a potentialas a new medicament for prevention or treatment of pain, stroke, cerebral ischemia, alcohol addiction, alcoholism, kidney disease, addictive disorder caused by analgesic or tolerance disorder caused by analgesic.

  该发明属于医药和化学工业领域，涉及一种4,4-二苯基哌啶化合物或其药用可接受盐，包括该化合物的药物组合物及其用途。具体而言，该发明涉及一种式I的化合物或其药用可接受盐，以及包括该化合物或其药用可接受盐的药物组合物。在本发明中，该化合物或其药用可接受盐和药物组合物在阻断N-型钙通道方面具有显著活性，并具有良好的药代动力学性质，可以有效缓解疼痛，并具有作为预防或治疗疼痛、中风、脑缺血、酒精成瘾、酗酒、肾病、镇痛剂引起的成瘾障碍或镇痛剂引起的耐受障碍的新药物的潜力。