3,4-dihydro-2-isopropyl-3-thioxo-2H-1,4-benzoxazine-4-acetic acid | 112808-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3,4-dihydro-2-isopropyl-3-thioxo-2H-1,4-benzoxazine-4-acetic acid
• 英文别名: (2-isopropyl-3-thioxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)acetic acid；2-(2-propan-2-yl-3-sulfanylidene-1,4-benzoxazin-4-yl)acetic acid
• CAS: 112808-25-0
• 化学式: C₁₃H₁₅NO₃S
• 分子量: 265.333
• InChiKey: NBARDBHMPZJJHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2-isopropyl-3-thioxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)acetic acid methyl ester 在 sodium hydroxide 作用下， 以 methanol-dioxane 、 正己烷 为溶剂， 生成 3,4-dihydro-2-isopropyl-3-thioxo-2H-1,4-benzoxazine-4-acetic acid
  参考文献：
  名称：

  Thiolactam-n-acetic acid derivatives

  摘要：

  通式化合物：##STR1## 其中，R1和R2相同或不同，为氢、卤素、低级烷基、环烷基、低级烷氧基、三氟甲基或苯基烷氧基，其苯环可被一至三个选自卤素、低级烷基、低级烷氧基、亚甲二氧基和三氟甲基的取代基所取代；R3为氢或甲基；R4为羧基或酯化的羧基；X为氧或硫，或其盐。这些化合物具有醛糖还原酶抑制和血小板聚集抑制活性，可作为药物用于预防和治疗糖尿病并发症，如糖尿病性白内障、视网膜病变、肾病变和神经病变。

  公开号：

  US04771050A1

文献信息

• Studies on antidiabetic agents. IX. A new aldose reductase inhibitor, AD-5467, and related 1,4-benzoxazine and 1,4-benzothiazine derivatives: Synthesis and biological activity.
  作者：Hiroyuki TAWADA、Yasuo SUGIYAMA、Hitoshi IKEDA、Yujiro YAMAMOTO、Kanji MEGURO

  DOI：10.1248/cpb.38.1238

  日期：——

  N-Acetic acid derivatives (I) of 2-substituted 1, 4-benzoxazines and benzothiazines were designed and synthesized for evaluation as new aldose reductase inhibitors. In general, 3-thioxo derivatives were more potent inhibitors of aldose reductase from human placenta in vitro than the corresponding 3-oxo derivatives. While many compounds (I) were not very effective in inhibiting sorbitol accumulation in the rat sciatic nerve in vivo, the 3-thioxo compounds bearing an isopropyl group at the 2-position showed highly potent activity in the in vivo assay. Compound 46 (AD-5467) was selected from this series as a candidate for further development.

  N-乙酸衍生物（I）的2-取代基1,4-苯并恶嗪和苯并噻嗪被设计合成，以评估其作为新型醛糖还原酶抑制剂的潜力。一般而言，3-硫代羰基衍生物在体外对人胎盘醛糖还原酶的抑制活性比相应的3-氧代衍生物更强。虽然许多化合物（I）在体内对大鼠坐骨神经山梨醇积累的抑制作用并不十分有效，但在体内试验中，2-位带有异丙基的3-硫代羰基化合物显示出极强的活性。从这一系列中选出化合物46（AD-5467）作为进一步开发的候选药物。
• Thiolactam-n-acetic acid derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04771050A1

  公开（公告）日：1988-09-13

  Compounds of the general formula: ##STR1## wherein, R.sup.1 and R.sup.2 are, the same or different, hydrogen, a halogen, a lower alkyl, a cycloalkyl, a lower alkoxy, trifluoromethyl or a phenylalkyloxy whose phenyl ring may be substituted by one to three substituents selected from the group consisting of a halogen, a lower alkyl, a lower alkoxy, methylenedioxy and trifluoromethyl; R.sup.3 is hydrogen or methyl; R.sup.4 is carboxyl or an esterified carboxyl; and X is oxygen or sulfur, or a salt thereof. These compounds possess aldose reductase inhibitory and platelet aggregation inhibitory activities, and are of use as drugs for prevention and treatment of diabetic complications such as diabetic cataract, retinophathy, nephropathy, and neuropathy.

  通式化合物：##STR1## 其中，R1和R2相同或不同，为氢、卤素、低级烷基、环烷基、低级烷氧基、三氟甲基或苯基烷氧基，其苯环可被一至三个选自卤素、低级烷基、低级烷氧基、亚甲二氧基和三氟甲基的取代基所取代；R3为氢或甲基；R4为羧基或酯化的羧基；X为氧或硫，或其盐。这些化合物具有醛糖还原酶抑制和血小板聚集抑制活性，可作为药物用于预防和治疗糖尿病并发症，如糖尿病性白内障、视网膜病变、肾病变和神经病变。
• CARBOXYLIC ACID COMPOUND AND USE THEREOF
  申请人：Japan Tobacco, Inc.

  公开号：EP1985297A1

  公开（公告）日：2008-10-29

  Provision of a superior URAT1 activity inhibitor effective for the treatment and the like of a pathology involving uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urinary lithiasis, renal dysfunction, coronary heart disease, ischemic cardiac diseases and the like. A URAT1 activity inhibitor containing a compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient: wherein each symbol is as defined in the specification.

  提供一种优异的URAT1活性抑制剂，有效治疗涉及尿酸的病症，如高尿酸血症、痛风性头痛、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾、尿路结石、肾功能障碍、冠心病、缺血性心脏病等。 一种含有下式[1]代表的化合物或其药学上可接受的盐或其溶液作为活性成分的 URAT1 活性抑制剂： 其中各符号如说明书中所定义。
• Thiolactam-N-acetic acid derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0243018B1

  公开（公告）日：1990-10-24
• MEHGURO, KANDZI;IKEHDA, MAMORU;YAMAMOTO, YUDZIRO
  作者：MEHGURO, KANDZI、IKEHDA, MAMORU、YAMAMOTO, YUDZIRO

  DOI：——

  日期：——