[(2S)-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol | 502434-88-0

• 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: [(2S)-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol
• 英文别名: (2S)-2-hydroxymethyl-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazine；[(2S)-7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazin-2-yl]methanol
• CAS: 502434-88-0
• 化学式: C₁₀H₁₂FNO₂
• 分子量: 197.209
• InChiKey: HYDACOPHVFEZCL-QMMMGPOBSA-N

物化性质

• 沸点：
  329.9±42.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(2S)-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol 在 吗啉 、 四(三苯基膦)钯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 1-(4-((2S)-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid
  参考文献：
  名称：

  Discovery of orally active prostaglandin D2 receptor antagonists

  摘要：

  A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D-2 (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.039
• 作为产物：
  描述：

  2,4-二氟苯胺 在 吡啶 、 potassium tert-butylate 、 苄基三乙基氯化铵 、 水 、 sodium naphthalenide 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 34.0h， 生成 [(2S)-7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol
  参考文献：
  名称：

  发现了一类新型的，有效的，选择性的和口服活性的前列腺素D2受体拮抗剂。

  摘要：

  提出了发现一系列N-（对烷氧基）苯甲酰基-2-甲基吲哚-4-乙酸类似物的过程，因为这些化合物代表了一类新的强效，选择性和口服活性前列腺素D2（PGD2）受体拮抗剂。这些化合物大多数在cAMP形成分析中表现出较强的PGD2受体结合和PGD2受体拮抗作用。口服时，这些新的拮抗剂可显着抑制过敏性炎症反应，例如PGD2诱导或OVA诱导的血管通透性增加。还讨论了结构活动关系（SAR）数据。

  DOI：

  10.1016/j.bmc.2004.07.048

文献信息

• Discovery of a new class of potent, selective, and orally active prostaglandin D2 receptor antagonists
  作者：Kazuhiko Torisu、Kaoru Kobayashi、Maki Iwahashi、Yoshihiko Nakai、Takahiro Onoda、Toshihiko Nagase、Isamu Sugimoto、Yutaka Okada、Ryoji Matsumoto、Fumio Nanbu、Shuichi Ohuchida、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2004.07.048

  日期：2004.10

  acetic acid analogs is presented since these compounds represent a new class of potent, selective, and orally active prostaglandin D2 (PGD2) receptor antagonists. Most of these compounds exhibit strong PGD2 receptor binding and PGD2 receptor antagonism in cAMP formation assays. When given orally, these new antagonists dramatically suppress allergic inflammatory responses, such as the PGD2-induced or

  提出了发现一系列N-（对烷氧基）苯甲酰基-2-甲基吲哚-4-乙酸类似物的过程，因为这些化合物代表了一类新的强效，选择性和口服活性前列腺素D2（PGD2）受体拮抗剂。这些化合物大多数在cAMP形成分析中表现出较强的PGD2受体结合和PGD2受体拮抗作用。口服时，这些新的拮抗剂可显着抑制过敏性炎症反应，例如PGD2诱导或OVA诱导的血管通透性增加。还讨论了结构活动关系（SAR）数据。
• Indole derivatives, process for producing the same and drugs containing the same as the active ingredient
  申请人：Torisu Kazuhiko

  公开号：US20050004096A1

  公开（公告）日：2005-01-06

  Indole derivatives represented by formula (I) wherein all symbols represent the same as that in specification), production methods thereof, and DP receptor antagonist comprising them as active ingredients. Since the compounds of formula (I) binds and antagonizes to DP receptor, they are useful for the prevention and/or treatment against allergic diseases, diseases accompanied with itching, secondary diseases generated by behaviors caused by itching, inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis.

  公式（I）所表示的吲哚衍生物（其中所有符号均与规范中相同），其生产方法以及包含它们作为活性成分的DP受体拮抗剂。由于公式（I）中的化合物结合并拮抗DP受体，因此它们对于预防和/或治疗过敏性疾病、伴随瘙痒的疾病、由瘙痒引起的行为所致的继发疾病、炎症、慢性阻塞性肺疾病、缺血再灌注障碍、脑血管疾病、风湿性关节炎并发的胸膜炎、溃疡性结肠炎等具有用处。
• INDOLE DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1424325A1

  公开（公告）日：2004-06-02

  Indole derivatives represented by formula (I)    wherein all symbols represent the same as that in specification), production methods thereof, and DP receptor antagonist comprising them as active ingredients. Since the compounds of formula (I) binds and antagonizes to DP receptor, they are useful for the prevention and/or treatment against allergic diseases, diseases accompanied with itching, secondary diseases generated by behaviors caused by itching, inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis.

  由式（I）代表的吲哚衍生物 其中所有符号均与说明书中的符号相同）的吲哚衍生物、其生产方法以及以它们为活性成分的 DP 受体拮抗剂。 由于式（I）化合物能结合并拮抗 DP 受体，因此可用于预防和/或治疗过敏性疾病、伴随瘙痒的疾病、由瘙痒引起的行为所导致的继发性疾病、炎症、慢性阻塞性肺病、缺血性再灌注疾病、脑血管疾病、类风湿性关节炎并发的胸膜炎、溃疡性结肠炎。
• US7153852B2
  申请人：——

  公开号：US7153852B2

  公开（公告）日：2006-12-26
• Discovery of orally active prostaglandin D2 receptor antagonists
  作者：Kazuhiko Torisu、Kaoru Kobayashi、Maki Iwahashi、Yoshihiko Nakai、Takahiro Onoda、Toshihiko Nagase、Isamu Sugimoto、Yutaka Okada、Ryoji Matsumoto、Fumio Nanbu、Shuichi Ohuchida、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmcl.2004.07.039

  日期：2004.10

  A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D-2 (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented. (C) 2004 Elsevier Ltd. All rights reserved.