2,6-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoic acid | 1116624-25-9

• 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: 2,6-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoic acid
• 英文别名: 2,6-dimethyl-4-(((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy)benzoic acid；2,6-dimethyl-4-[[(2S)-4-methyl-2,3-dihydro-1,4-benzoxazin-2-yl]methoxy]benzoic acid
• CAS: 1116624-25-9
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: WJDPPVZSPFUMHJ-HNNXBMFYSA-N

物化性质

• 沸点：
  510.4±50.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoic acid 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 1-{4-chloro-3-[(2,6-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoyl)amino]phenyl}cyclopropanecarboxylic acid
  参考文献：
  名称：

  Discovery of new orally active prostaglandin D2 receptor antagonists

  摘要：

  To identify an orally available drug candidate, a series of 3-benzoylaminophenylacetic acids were synthesized and evaluated as prostaglandin D-2 (PGD(2)) receptor antagonists. Some of the compounds tested were found to exhibit excellent inhibitory activity against cAMP accumulation in human platelet rich plasma (hPRP), which is one of the indexes of DP antagonism. The optimization process including improvement of the physicochemical properties such as solubility, which may result in an improved pharmacokinetic (PK) profile, is presented. Optimized compounds were studied for their pharmacokinetics and in vivo potential. A structure-activity relationship study is also presented. Some of the test compounds were found to have in vivo efficacy towards the inhibition of PGD(2)-induced and OVA-induced vascular permeability in guinea pig conjunctiva. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.065
• 作为产物：
  描述：

  [(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methyl 4-methylbenzenesulfonate 在 caesium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙二醇乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2,6-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoic acid
  参考文献：
  名称：

  Discovery of new orally active prostaglandin D2 receptor antagonists

  摘要：

  To identify an orally available drug candidate, a series of 3-benzoylaminophenylacetic acids were synthesized and evaluated as prostaglandin D-2 (PGD(2)) receptor antagonists. Some of the compounds tested were found to exhibit excellent inhibitory activity against cAMP accumulation in human platelet rich plasma (hPRP), which is one of the indexes of DP antagonism. The optimization process including improvement of the physicochemical properties such as solubility, which may result in an improved pharmacokinetic (PK) profile, is presented. Optimized compounds were studied for their pharmacokinetics and in vivo potential. A structure-activity relationship study is also presented. Some of the test compounds were found to have in vivo efficacy towards the inhibition of PGD(2)-induced and OVA-induced vascular permeability in guinea pig conjunctiva. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.065

文献信息

• Phenylacetic acid compound
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US08318729B2

  公开（公告）日：2012-11-27

  A compound represented by formula (I), wherein R1 represents a hydrogen atom, etc., R2 and R3 each independently represents a hydrogen atom, optionally oxidized C1-4 alkyl group or optionally protected hydroxyl group, or R2 and R3 taken together represent optionally oxidized C2-5 alkylene group, R4 represents an optionally oxidized C1-6 alkyl group, etc., R5 represents an optionally oxidized C1-6 alkyl group, etc., R6 represents an optionally oxidized C1-6 alkyl group, etc., m represents 0 or an integer from 1 to 3, n represents 0 or an integer from 1 to 4, and i represents 0 or an integer from 1 to 7.

  化合物的化学式为（I），其中R1代表氢原子，R2和R3各自独立地代表氢原子、可选的氧化的C1-4烷基或可选的保护羟基，或者R2和R3结合代表可选的氧化的C2-5亚烷基，R4代表可选的氧化的C1-6烷基，R5代表可选的氧化的C1-6烷基，R6代表可选的氧化的C1-6烷基，m代表0或1到3的整数，n代表0或1到4的整数，i代表0或1到7的整数。
• Phenylacetic Acid Compound
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20140357630A1

  公开（公告）日：2014-12-04

  A compound represented by formula (I), wherein R 1 represents a hydrogen atom, etc., R 2 and R 3 each independently represents a hydrogen atom, optionally oxidized C1-4 alkyl group or optionally protected hydroxyl group, or R 2 and R 3 taken together represent optionally oxidized C2-5 alkylene group, R 4 represents an optionally oxidized C1-6 alkyl group, etc., R 5 represents an optionally oxidized C1-6 alkyl group, etc., R 6 represents an optionally oxidized C1-6 alkyl group, etc., m represents 0 or an integer from 1 to 3, n represents 0 or an integer from 1 to 4, and i represents 0 or an integer from 1 to 7.

  化合物的化学式为（I），其中R1代表氢原子等，R2和R3各自独立地代表氢原子，可选的氧化C1-4烷基或可选择保护的羟基，或者R2和R3一起代表可选的氧化C2-5亚烷基，R4代表可选的氧化C1-6烷基等，R5代表可选的氧化C1-6烷基等，R6代表可选的氧化C1-6烷基等，m代表0或1至3的整数，n代表0或1至4的整数，i代表0或1至7的整数。
• PHENYLACETIC ACID COMPOUND
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2177513B1

  公开（公告）日：2015-07-01
• US8318729B2
  申请人：——

  公开号：US8318729B2

  公开（公告）日：2012-11-27
• US8476266B2
  申请人：——

  公开号：US8476266B2

  公开（公告）日：2013-07-02