2,3,6-trimethylquinazolin-4(3H)-one | 63190-58-9

• 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: 2,3,6-trimethylquinazolin-4(3H)-one
• 英文别名: 2,3,6-Trimethyl-4-oxo-3,4-dihydrochinazolin；2,3,6-trimethylquinazolin-4-one；2,3,6-trimethyl-3H-quinazolin-4-one；3,4-dihydro-2,3,6-trimethylquinazolin-4-one
• CAS: 63190-58-9
• 化学式: C₁₁H₁₂N₂O
• 分子量: 188.229
• InChiKey: BMWFOQLEZCMJPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,3,6-trimethylquinazolin-4(3H)-one 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 生成 6-(bromomethyl)-2,3-dimethylquinazolin-4-one
  参考文献：
  名称：

  Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methylprop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)

  摘要：

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.

  DOI：

  10.1021/jm101145b
• 作为产物：
  描述：

  N-Acetyl-5,N-dimethyl-2-nitro-benzamide 在 十二羰基三钌 一氧化碳 作用下， 以 1,4-二氧六环 为溶剂， 140.0 ℃ 、4.05 MPa 条件下， 反应 16.0h， 以92%的产率得到2,3,6-trimethylquinazolin-4(3H)-one
  参考文献：
  名称：

  Transition-metal complex-catalyzed reductive N-heterocyclization: synthesis of 4(3H)-quinazolinone derivatives from N-(2-nitrobenzoyl)amides

  摘要：

  Several ruthenium and platinum complexes smoothly catalyze the reductive N-heterocyclization of N-(2-nitrobenzoyl)amides under carbon monoxide pressure to afford the corresponding 4(3H)-quinazolinone derivatives, including some quinazolinone alkaloids, in good yields.

  DOI：

  10.1021/jo00054a008

文献信息

• Cp*Co^III-catalyzed formal [4+2] cycloaddition of benzamides to afford quinazolinone derivatives
  作者：Jingshu Yang、Xiao Hu、Zijie Liu、Xueyuan Li、Yi Dong、Gang Liu

  DOI：10.1039/c9cc07173c

  日期：——

  A Cp*CoIII-catalyzed arene C–H bond amidation/annulation of benzamides was developed to afford quinazolinone derivatives in one-pot with high yields and broad substrate scope. This method could be applied to the synthesis of quinazolinone drugs and late-stage modification of natural products.

  开发了一种由Cp * Co III催化的苯甲酰胺C / H键酰胺化/环化反应，可一锅制得喹唑啉酮衍生物，并具有高收率和广泛的底物范围。该方法可用于喹唑啉酮类药物的合成和天然产物的后期修饰。
• PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20140371246A1

  公开（公告）日：2014-12-18

  The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts or isomers thereof, in which n, m, R 1 , R 2 , R 4 , and R 3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts or isomers thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.

  本公开提供了式（I）的磷脂酰肌醇3-激酶（PI3K）抑制剂，或其药用盐或异构体，其中n、m、R1、R2、R4和R3如本文所定义。这些化合物可用于治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ。本公开还提供了包括式（I）的化合物、药用盐或异构体的药物组合物，以及使用这些化合物和组合物治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ的方法。
• Quinazoline derivatives possessing anti-tumor activity
  申请人：Imperial Chemical Industries PLC

  公开号：US05089499A1

  公开（公告）日：1992-02-18

  The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms; R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, halogenoalkyl or cyanoalkyl each of up to 6 carbon atoms; Ar is phenylene or heterocyclene; L is a group of the formula --CO.NH--, --NH.CO--, --CO.NR.sup.3 --, --NR.sup.3. CO--, --CH.dbd.CH--, --CH.sub.2 O--, --OCH.sub.2, --CH.sub.2 S--, --SCH.sub.2 --, --CO.CH.sub.2 --, --CH.sub.2.CO-- or --CO.O--, wherein R.sup.3 is alkyl of up to 6 carbon atoms; and Y is aryl or heteroaryl or a hydrogenated derivative thereof: or Y is a group of the formula --A--Y.sup.1 in which A is alkylene, cycloalkylene, alkenylene or alkynylene each of up to 6 carbon atoms and Y.sup.1 is aryl or heteroaryl or a hydrogenated derivative thereof; or a pharmaceutically-acceptable salt thereof.

  该发明涉及喹唑啉衍生物或其药用盐，具有抗肿瘤活性；以及其制备方法；以及含有它们的药物组合物。 该发明提供了一种喹唑啉的结构式：其中R.sup.1是氢或氨基，或每个最多6个碳原子的烷基或烷氧基；或R.sup.1是取代的每个最多3个碳原子的烷基或烷氧基；R.sup.2是氢，烷基，烯基，炔基，羟基烷基，卤代烷基或氰基烷基，每个最多6个碳原子；Ar是苯基或杂环烯；L是下式的基团：--CO.NH--，--NH.CO--，--CO.NR.sup.3--，--NR.sup.3.CO--，--CH.dbd.CH--，--CH.sub.2O--，--OCH.sub.2--，--CH.sub.2S--，--SCH.sub.2--，--CO.CH.sub.2--，--CH.sub.2.CO--或--CO.O--，其中R.sup.3是最多6个碳原子的烷基；Y是芳基或杂芳基或其氢化衍生物：或Y是下式的基团：--A--Y.sup.1，其中A是烷基，环烷基，烯基或炔基，每个最多6个碳原子，Y.sup.1是芳基或杂芳基或其氢化衍生物；或其药用盐。
• PLATELET ADP RECEPTOR INHIBITORS
  申请人：Scarborough Robert M.

  公开号：US20120149688A1

  公开（公告）日：2012-06-14

  Novel compounds of formulae (I) and (VIII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.

  式(I)和(VIII)的新化合物，其中更特别地包括磺酰脲衍生物、磺酰硫脲衍生物、磺酰胍衍生物、磺酰氰基胍衍生物、硫代酰基磺酰胺衍生物和酰基磺酰胺衍生物，它们是有效的血小板ADP受体抑制剂。这些衍生物可用于各种药物组合物中，特别是对于预防和/或治疗心血管疾病，特别是与血栓形成相关的疾病非常有效。本发明还涉及一种用于预防或治疗哺乳动物中的血栓形成的方法，包括给予化合物(I)到(VIII)的治疗有效量或其药学上可接受的盐。
• BICYCLIC HETEROCYCLIC DERIVATIVE
  申请人：Nakahira Hiroyuki

  公开号：US20110190278A1

  公开（公告）日：2011-08-04

  The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt thereof, being useful as a renin inhibitor. [wherein R 1a is halogen, etc.; R 1m is H, etc.; G 1 is —N(R 1b )—, etc.; G 2 is —CO—, etc.; G 3 is —C(R 1c )(R 1d )—, etc.; G 4 is oxygen, etc.; R 1b is optionally substituted C 1-6 alkyl, etc.; R 1c and R 1d are independently the same or different, H, etc.; R 3 is H, optionally substituted C 1-6 alkyl, etc.; R 3a , R 3b , R 3 c and R 3d are independently the same or different, and a group: -A-B (said A is single bond, etc., and said B is H, etc.), etc.; and n is 1, etc.]

  本发明涉及以下式（I）的化合物或其药学上可接受的盐，其可用作肾素抑制剂。[其中，R1a是卤素等；R1m是H等；G1是—N（R1b）—等；G2是—CO—等；G3是—C（R1c）（R1d）—等；G4是氧等；R1b是可选取代的C1-6烷基等；R1c和R1d独立选择为H等；R3是H、可选取代的C1-6烷基等；R3a、R3b、R3c和R3d独立选择为相同或不同的基团：-A-B（其中A是单键等，B是H等）等；n为1等。]