3-(4-bromo-2-fluorobenzyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione | 122185-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-(4-bromo-2-fluorobenzyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
• 英文别名: 3-[(4-bromo-2-fluorophenyl)methyl]-5-methyl-1H-thieno[2,3-d]pyrimidine-2,4-dione
• CAS: 122185-82-4
• 化学式: C₁₄H₁₀BrFN₂O₂S
• 分子量: 369.214
• InChiKey: MFYSHKCKBIAERG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-bromo-2-fluorobenzyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione 在 盐酸 、 sodium hydride 作用下， 以 溶剂黄146 为溶剂， 反应 28.0h， 生成 1-carboxymethyl-3-(4-bromo-2-fluorobenzyl)-5-methylthieno[2,3-d]pyrimidin-2,4(1H, 3H)-dione
  参考文献：
  名称：

  Syntheses of substituted 2,4-dioxo-thienopyrimidin-1-acetic acids and their evaluation as aldose reductase inhibitors

  摘要：

  A series of 2,4-dioxo-thieno[2,3-d], [3,2-d] and [3,4-d]pyrimidin-1-acetic acids (2) with a benzyl moiety at the N-3 position were prepared and tested in vitro for aldose reductase inhibitory activity against partially purified enzyme from rat lens. Some of these compounds were also evaluated for inhibition of sorbitol accumulation in the sciatic nerve or lens of streptozotocin-induced diabetic rats in vivo. Among the synthesized compounds, several showed potent aldose reductase inhibitory activity with IC50s in the 10(-8) M range. Particularly, the potencies of non-substituted thieno- (2a and 2aa), 5-methylthieno- (2c), 5,6-dimethylthieno-(2g), 6-isopropylthieno- (2j and 2k), 6-chlorothienopyrimidine (2q) and benzothienopyrimidine (2ac) analogs were approximately equipotent to FK-366 (1A) and Ponalrestat (1B) as references. Although most compounds were inactive in vivo, 2 compounds, 2k and 2q, possessed moderate in vivo activity.

  DOI：

  10.1016/0223-5234(93)90112-r
• 作为产物：
  描述：

  2-氨基-4-甲基-噻吩-3-羧酸乙酯 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 3-(4-bromo-2-fluorobenzyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Syntheses of substituted 2,4-dioxo-thienopyrimidin-1-acetic acids and their evaluation as aldose reductase inhibitors

  摘要：

  A series of 2,4-dioxo-thieno[2,3-d], [3,2-d] and [3,4-d]pyrimidin-1-acetic acids (2) with a benzyl moiety at the N-3 position were prepared and tested in vitro for aldose reductase inhibitory activity against partially purified enzyme from rat lens. Some of these compounds were also evaluated for inhibition of sorbitol accumulation in the sciatic nerve or lens of streptozotocin-induced diabetic rats in vivo. Among the synthesized compounds, several showed potent aldose reductase inhibitory activity with IC50s in the 10(-8) M range. Particularly, the potencies of non-substituted thieno- (2a and 2aa), 5-methylthieno- (2c), 5,6-dimethylthieno-(2g), 6-isopropylthieno- (2j and 2k), 6-chlorothienopyrimidine (2q) and benzothienopyrimidine (2ac) analogs were approximately equipotent to FK-366 (1A) and Ponalrestat (1B) as references. Although most compounds were inactive in vivo, 2 compounds, 2k and 2q, possessed moderate in vivo activity.

  DOI：

  10.1016/0223-5234(93)90112-r

文献信息

• Thienopyrimidine derivaties as aldose-reductase inhibitors
  申请人：Taiho Pharmaceutical Company, Limited

  公开号：US04898867A1

  公开（公告）日：1990-02-06

  The present invention provides thienopyrimidine derivatives of the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represent hydrogen, halogen, lower alkyl, cycloalkyl or phenyl, R.sub.1 and R.sub.2 taken together may form a ring of an alkylene chain, R.sub.3 represents lower alkyl or a group of the formula ##STR2## (in which R.sub.4 is a lower alkyl, lower alkoxy or halogen, m is 0, 1 or 2, and R.sub.5 is hydrogen or halogen) and Z is oxygen or sulfur, or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing them as an active principle and aldose-reductase inhibitors.

  本发明提供了式（I）的噻唑嘧啶衍生物##STR1##其中，R.sub.1和R.sub.2相同或不同，分别代表氢、卤素、较低的烷基、环烷基或苯基，R.sub.1和R.sub.2结合在一起可以形成一个烷基链的环，R.sub.3代表较低的烷基或式##STR2##（其中，R.sub.4是较低的烷基、较低的烷氧基或卤素，m为0、1或2，R.sub.5为氢或卤素），Z为氧或硫，或其药学上可接受的盐，以及包含它们作为活性原理的药物组合物和醛糖还原酶抑制剂。
• THIENOPYRIMIDINE DERIVATIVES
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP0335979A1

  公开（公告）日：1989-10-11

  Thienopyrimidine derivatives represented by general formula (I), wherein R1 and R2, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkyl group, a cyclic alkyl group or a phenyl group, or R1 and R2 may be bound to each other to form an alkylene chain for forming a ring, R3 represents a lower alkyl group or a group of formula (II) (wherein R4 represents a lower alkyl group, a lower alkoxy group or a halogen atom, m represents 0, 1 or 2 and Rs represents a hydrogen atom or a halogen atom) or pharmaceutically acceptable salts thereof, a pharmacological composition containing the same as effective ingredient, and an aldose reductase inhibitor are disclosed.

  由通式(I)代表的噻吩嘧啶衍生物，其中 R1 和 R2 可以相同或不同，各自代表氢原子、卤素原子、低级烷基、环状烷基或苯基，或者 R1 和 R2 可以相互结合形成亚烷基链以形成环、R3 代表低级烷基或式（II）基团（其中 R4 代表低级烷基、低级烷氧基或卤素原子，m 代表 0、1 或 2，Rs 代表氢原子或卤素原子）或其药学上可接受的盐、含有其作为有效成分的药物组合物以及醛糖还原酶抑制剂。
• Ogawva K., Yamawaki I., Matsusita Y. I., Nomura N., Kador P. F., Kinoshit+, Eur. I. Med. Chem, 28 (1993) N 10, S 769-781
  作者：Ogawva K., Yamawaki I., Matsusita Y. I., Nomura N., Kador P. F., Kinoshit+

  DOI：——

  日期：——
• US4898867A
  申请人：——

  公开号：US4898867A

  公开（公告）日：1990-02-06
• Syntheses of substituted 2,4-dioxo-thienopyrimidin-1-acetic acids and their evaluation as aldose reductase inhibitors
  作者：K Ogawva、I Yamawaki、YI Matsusita、N Nomura、PF Kador、JH Kinoshita

  DOI：10.1016/0223-5234(93)90112-r

  日期：1993.1

  A series of 2,4-dioxo-thieno[2,3-d], [3,2-d] and [3,4-d]pyrimidin-1-acetic acids (2) with a benzyl moiety at the N-3 position were prepared and tested in vitro for aldose reductase inhibitory activity against partially purified enzyme from rat lens. Some of these compounds were also evaluated for inhibition of sorbitol accumulation in the sciatic nerve or lens of streptozotocin-induced diabetic rats in vivo. Among the synthesized compounds, several showed potent aldose reductase inhibitory activity with IC50s in the 10(-8) M range. Particularly, the potencies of non-substituted thieno- (2a and 2aa), 5-methylthieno- (2c), 5,6-dimethylthieno-(2g), 6-isopropylthieno- (2j and 2k), 6-chlorothienopyrimidine (2q) and benzothienopyrimidine (2ac) analogs were approximately equipotent to FK-366 (1A) and Ponalrestat (1B) as references. Although most compounds were inactive in vivo, 2 compounds, 2k and 2q, possessed moderate in vivo activity.