5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone | 437995-22-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone
• 英文别名: E67FD8JH4V；5-chloro-2-[3-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)propyl]-3H-quinazolin-4-one
• CAS: 437995-22-7
• 化学式: C₂₂H₂₂ClN₃O
• 分子量: 379.889
• InChiKey: QJGMBDBIOLISMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone
  参考文献：
  名称：

  合理的方法来发现聚（ADP-核糖）聚合酶的口服活性和脑可穿透的喹唑啉酮抑制剂。

  摘要：

  已发现一类新型的喹唑啉酮衍生物作为有效的聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。成功的关键是应用合理的发现策略，包括基于结构的设计，组合化学和经典SAR，以提高药效和生物利用度。新抑制剂被显示与NAD +的烟酰胺-核糖结合位点（NI位点）和腺苷-核糖结合位点（AD位点）结合。

  DOI：

  10.1021/jm0499256

文献信息

• TARGETING ABNORMAL DNA REPAIR IN THERAPY-RESISTANT BREAST AND PANCREATIC CANCERS
  申请人：STC.UNM

  公开号：US20160051517A1

  公开（公告）日：2016-02-25

  In one embodiment, the invention provides a method of treating a subject suffering from a breast cancer tumor which is non-responsive or intrinsically resistant to anti-estrogen therapy comprising administering a therapeutically effective amount of an inhibitor of alternative (ALT) non-homologous end joining (NHEJ) factor to the subject. In another embodiment the invention provides a method of treating a subject who suffers from a pancreatic cancer which is non-responsive to chemotherapy and/or radiation comprising co-administering a therapeutically effective amount of PARP1 inhibitor and a DNA ligase IIIα inhibitor to the subject. Related diagnostic methods, nucleic acid arrays, devices and kits are also provided.

  在一个实施例中，本发明提供了一种治疗患有对抗雌激素疗法无反应或内在抵抗的乳腺癌肿瘤的受试者的方法，该方法包括向受试者施用治疗有效量的替代（ALT）非同源末端连接（NHEJ）因子抑制剂。在另一个实施例中，本发明提供了一种治疗患有对化疗和/或放疗无反应的胰腺癌的受试者的方法，该方法包括联合施用治疗有效量的PARP1抑制剂和DNA连接酶IIIα抑制剂给受试者。还提供了相关的诊断方法、核酸阵列、设备和试剂盒。
• Quinazolinone derivatives
  申请人：——

  公开号：US20040077667A1

  公开（公告）日：2004-04-22

  A quinazolinone derivatives having poly (adenosine 5′-diphaspho-ribose)polymerase (PARP) inhibotory activity represented by the formula (I), wherein R1 is optionally substituted cyclic amino groups or optionally substituted amino group, R2 is substituent, n means an integer from 0 to 4, and L is lower akkylene or lower alkenylene, or its prodrug, or their salts. 1

  一种具有聚(腺苷酸二磷酸核糖)聚合酶（PARP）抑制活性的喹唑啉酮衍生物，其化学式为（I），其中R1是可选取代的环氨基或可选取代的氨基基团，R2是取代基，n表示0至4的整数，L是低级别的取代基或低级别的烯基取代基，或其前药或盐。
• [EN] QUINAZOLINONE DERIVATIVES<br/>[FR] DERIVES DE QUINAZOLINONE
  申请人：FUJISAWA PHARMACEUTICAL CO

  公开号：WO2002048117A1

  公开（公告）日：2002-06-20

  A quinazolinone derivatives having poly(adenosine 5'-diphaspho-ribose)polymerase (PARP) inhibotory activity represented by the formula (I), wherein R1 is optionally substituted cyclic amino groups or optionally substituted amino group, R2 is substituent, n means an integer from 0 to 4, and L is lower akkylene or lower alkenylene, or its prodrug, or their salts.

  一种喹唑啉酮衍生物，具有聚腺苷酸二磷酸核糖聚合酶（PARP）抑制活性，其化学式表示为（I），其中R1是可选取代的环氨基或可选取代的氨基基团，R2是取代基，n表示0到4的整数，L是低级脂肪基或低级烯基，或其前药或其盐。
• Compositions for treating cancer
  申请人：Fundacio Centre de Regulacio Genomica

  公开号：EP2930238A1

  公开（公告）日：2015-10-14

  The present invention relates to a Nudix5 inhibitor for use in the treatment and/or prevention of cancer in a subject and pharmaceutical compositions comprising a therapeutically effective amount of a Nudix5 inhibitor and a pharmaceutically acceptable excipient or carrier, and to a pharmaceutical composition comprising a therapeutically effective amount of a composition comprising a Nudix5 inhibitor and at least a second antitumor agent and a pharmaceutically acceptable excipient or carrier. Furthermore, the invention relates to a method for assaying the activity of Nudix5 comprising assaying the formation of ATP, and to a method for identifying a compound potentially useful for treating and/or preventing cancer comprising assaying the activity of Nudix5 in the presence of said compound.

  本发明涉及一种用于治疗和/或预防受试者癌症的Nudix5抑制剂和药物组合物，该药物组合物包含治疗有效量的Nudix5抑制剂和药学上可接受的赋形剂或载体，还涉及一种药物组合物，该药物组合物包含治疗有效量的组合物，该组合物包含Nudix5抑制剂和至少第二种抗肿瘤剂以及药学上可接受的赋形剂或载体。此外，本发明还涉及一种检测 Nudix5 活性的方法，该方法包括检测 ATP 的形成；本发明还涉及一种鉴定可能用于治疗和/或预防癌症的化合物的方法，该方法包括在所述化合物存在的情况下检测 Nudix5 的活性。
• Synergistic enhancement of 5-fluorouracil cytotoxicity by deoxyuridine analogs in cancer cells
  申请人：STC.UNM

  公开号：US10086010B2

  公开（公告）日：2018-10-02

  In one embodiment, the invention provides a method of treating a subject who suffers from a neoplasm (including a cancer such as a radiotherapeutic-resistant cancer) by administering to the subject a therapeutically effective amount of (a) 5-formyl-2′-deoxyuridine (fdU or foUdR) or a 5-formyl-2′-deoxyuridine derivative, optionally in combination with 5-hydroxy-2′-deoxyuridine (hUdR); and (b) at least one composition selected from the group consisting of either 5-fluorouracil (5-FU), a 5-FU prodrug (e.g. 5-fluoro-2′-deoxyuridine (FdU)) or 5-FU metabolite. In a preferred embodiment, a subject who suffers from colorectal cancer (CRC) or metastatic colorectal cancer (mCRC) is treated with a therapeutically-effective amount of fdU and either 5-FU or the 5-FU prodrug 5-fluoro-2′-deoxyuridine (FdU). Related pharmaceutical compositions are also provided.

  在一个实施方案中，本发明提供了一种治疗患有肿瘤（包括癌症，如放射治疗耐药癌症）的受试者的方法，该方法通过向受试者施用治疗有效量的(a)5-甲酰基-2′-脱氧尿苷（fdU或foUdR）或5-甲酰基-2′-脱氧尿苷衍生物，可选择与5-羟基-2′-脱氧尿苷（hUdR）结合使用；(b) 至少一种组合物，该组合物选自由 5-氟尿嘧啶（5-FU）、5-FU 原药（如例如，5-氟-2′-脱氧尿苷（FdU）或 5-FU 代谢物。在一个优选的实施方案中，用治疗有效量的fdU和5-FU或5-FU原药5-氟-2′-脱氧尿苷（FdU）治疗结直肠癌（CRC）或转移性结直肠癌（mCRC）患者。还提供了相关的药物组合物。