6-bromo-3-(pyridin-3-ylmethyl)quinazolin-4(3H)-one

• 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: 6-bromo-3-(pyridin-3-ylmethyl)quinazolin-4(3H)-one
• 英文别名: 6-bromo-3-(3-pyridylmethyl)-4 (3H)-quinazolinone；6-bromo-3-(pyridin-3-ylmethyl)quinazolin-4-one
• 化学式: C₁₄H₁₀BrN₃O
• 分子量: 316.157
• InChiKey: DHGIHAWZMYQIKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-fluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide 、 6-bromo-3-(pyridin-3-ylmethyl)quinazolin-4(3H)-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 4-fluoro-N-(2-methoxy-5-(4-oxo-3-(pyridin-3-ylmethyl)-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)phenylsulfonamide
  参考文献：
  名称：

  Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety

  摘要：

  In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl) phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3K alpha. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents. (c) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.11.027
• 作为产物：
  描述：

  3-氨甲基吡啶 、 原甲酸三乙酯 、 2-氨基-5-溴苯甲酸 在 碘 作用下， 以 乙醇 为溶剂， 以76.1%的产率得到6-bromo-3-(pyridin-3-ylmethyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety

  摘要：

  In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl) phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3K alpha. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents. (c) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.11.027

文献信息

• Benzamide platelet activating factor antagonists
  申请人：Mitsubishi Kasei Corporation

  公开号：US05401756A1

  公开（公告）日：1995-03-28

  Benzamide platelet activating factor antagonists of the following formula (I): ##STR1## wherein ##STR2## B, D: hydrogen atom, etc. E: pyridyl group, etc. n: integer from 0 to 2 R.sup.2 : R.sup.3 R.sup.4 N-- etc. (R.sup.3, R.sup.4 : optionally substituted C.sub.6 -C.sub.12 aryl group, etc.) ##STR3## optical antipodes thereof or pharmaceutically acceptable salts thereof, show excellent PAF antagonism and are effective for therapy and prophylaxis of diseases caused by PAF (bronchial asthma, nephritis, shocks, cardiac infarction, cerebral hemorrhage, ulcer, DIC, autoimmune diseases, thrombosis, etc.).

  苯甲酰胺血小板活化因子拮抗剂的化学式（I）如下：##STR1## 其中，##STR2## B，D：氢原子等。 E：吡啶基等。 n：整数，范围从0到2。 R.sup.2：R.sup.3 R.sup.4 N--等。（R.sup.3，R.sup.4：可选取代的C.sub.6-C.sub.12芳基等） ##STR3## 其光学对映体或药物可接受的盐，表现出优异的PAF拮抗作用，并对由PAF引起的疾病（支气管哮喘、肾炎、休克、心肌梗塞、脑出血、溃疡、DIC、自身免疫疾病、血栓形成等）的治疗和预防具有有效作用。
• Benza-triazinone derivatives
  申请人：Mitsubishi Kasei Corporation

  公开号：US05304556A1

  公开（公告）日：1994-04-19

  Benzamide derivatives of the following formula (I) ##STR1## [wherein R.sup.1 : ##STR2## B, D: hydrogen atom, etc. E: pyridyl group, etc. n: integer from 0 to 2 R.sup.2 : R.sup.3 R.sup.4 N-- etc. (R.sup.3,R.sup.4 : optionally substituted C.sub.6 -C.sub.14 aryl group, etc.) A; ##STR3## --CH.sub.2 --, --N.dbd.N--, --CH.dbd.N--, --N.dbd.CH--, --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --]. Optical antipodes thereof or pharmaceutically acceptable salts thereof, show excellent PAF antagonism and are effective for therapy and prophylaxis of diseases caused by PAF (bronchial asthma, nephritis, shocks, cardiac infarction, cerebral hemorrhage, ulcer, DIC, autoimmune diseases, thrombosis, etc.).

  以下是公式（I）的苯甲酰胺衍生物： 其中，R1： B，D：氢原子等 E：吡啶基等 n：0到2的整数 R2：R3R4N-等（R3，R4：可选择取代的C6-C14芳基等） A： --CH2--，--N= N--，--CH= N--，--N= CH--，--CH= CH--或--CH2--CH2--。 它们的光学对映体或药学上可接受的盐表现出良好的PAF拮抗作用，并且对于由PAF引起的疾病（支气管哮喘，肾炎，休克，心脏梗塞，脑出血，溃疡，DIC，自身免疫疾病，血栓形成等）的治疗和预防非常有效。
• Benzamide derivatives
  申请人：Mitsubishi Chemical Corporation

  公开号：EP0548934A1

  公开（公告）日：1993-06-30

  Benzamide derivatives of the following formula (I): [wherein R¹: B, D:hydrogen atom, etc. E:pyridyl group, etc. n:integer from 0 to 2 R²:R³R⁴N- etc. (R³, R⁴: optionally substituted C₆ - C₁₂ aryl group, etc.) A: -CH₂-, -N=H-, -CH=N-, -N=CH-, -CH=CH- or -CH₂-CH₂-]. optical antipodes thereof or pharmaceutically acceptable salts thereof, show excellent PAF antagonism and are effective for therapy and prophylaxis of diseases caused by PAF (bronchial asthma, nephritis, shocks, cardiac infarction, cerebral hemorrhage, ulcer, DIC, autoimmune diseases, thrombosis, etc.).

  下式(I)的苯甲酰胺衍生物： [其中 R¹： B、D:氢原子等 E:吡啶基等 n:0 至 2 的整数 R²:R³R⁴N- 等。 (R³、R⁴：任选取代的 C₆ - C₁₂ 芳基等。） A: -CH₂-、-N=H-、-CH=N-、-N=CH-、-CH=CH-或-CH₂-CH₂-]。 其光学抗原或其药学上可接受的盐类显示出优异的 PAF 拮抗作用，对治疗和预防 PAF 引起的疾病（支气管哮喘、肾炎、休克、心肌梗塞、脑出血、溃疡、DIC、自身免疫性疾病、血栓形成等）有效。
• US5304556A
  申请人：——

  公开号：US5304556A

  公开（公告）日：1994-04-19
• US5401756A
  申请人：——

  公开号：US5401756A

  公开（公告）日：1995-03-28