(4S)-4-benzyl-3-{(2R)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentanoyl}-1,3-oxazolidin-2-one | 856687-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S)-4-benzyl-3-{(2R)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentanoyl}-1,3-oxazolidin-2-one
• 英文别名: (4S)-4-benzyl-3-[(2R)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)-hydroxymethyl]-5-phenylpentanoyl]-1,3-oxazolidin-2-one
• CAS: 856687-67-7
• 化学式: C₃₁H₃₅NO₆
• 分子量: 517.622
• InChiKey: UAERFNWSUJWNON-IWVFXYMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S)-4-benzyl-3-{(2R)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentanoyl}-1,3-oxazolidin-2-one 在 2,6-二甲基吡啶 、 lithium aluminium tetrahydride 、 锂硼氢 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 sodium iodide 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 11.83h， 生成 (1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenylpentyl}-1H-pyrazol-4-yl)acetonitrile
  参考文献：
  名称：

  Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  Scaffold hopping from the amide group of lead compound ONO 7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA(1)) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPAI receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [H-3]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.

  DOI：

  10.1021/acsmedchemlett.7b00383
• 作为产物：
  描述：

  苯(甲)醛,3,5-二甲氧基-4-甲基- 、 (4S)-4-苄基-3-(5-苯基戊酰基)-1,3-恶唑烷-2-酮 在 三甲基氯硅烷 、 三乙胺 、 magnesium chloride 、 盐酸 作用下， 以 乙酸乙酯 、 甲醇 为溶剂， 反应 0.08h， 以87%的产率得到(4S)-4-benzyl-3-{(2R)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentanoyl}-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  Scaffold hopping from the amide group of lead compound ONO 7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA(1)) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPAI receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [H-3]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.

  DOI：

  10.1021/acsmedchemlett.7b00383

文献信息

• Compounds having lysophosphatidic acid receptor antagonism and uses thereof
  申请人：Tanaka Motoyuki

  公开号：US20070149595A1

  公开（公告）日：2007-06-28

  The present invention relates to a compound represented by formula (I): (wherein the symbols in formula were described in the description), a salt thereof, a solvate thereof or a prodrug thereof. Since the compound of the present invention binds to and is antagonistic to an LPA receptor (particularly, EDG-2), it is useful for prevention and/or treatment of urinary system disease (prostatic hypertrophy or neurogenic bladder dysfunction disease, spinal cord neoplasm, nucleous hernia, spinal canal stenosis, diseases caused by diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, and polyuria), carcinoma-associated disease, proliferative disease, inflammation system disease, immune system disease, disease by secretory dysfunction, brain-related disease and/or chronic disease.

  本发明涉及一种由式(I)表示的化合物：（其中式中的符号在说明中被描述），其盐，溶剂化物或前药。由于本发明的化合物与LPA受体（特别是EDG-2）结合并具有拮抗作用，因此它对预防和/或治疗泌尿系统疾病（前列腺增生或神经源性膀胱功能障碍疾病，脊髓肿瘤，核突出，脊柱管狭窄，由糖尿病引起的疾病，下尿路梗阻疾病，下尿路炎症性疾病和多尿症），癌症相关疾病，增殖性疾病，炎症系统疾病，免疫系统疾病，分泌功能障碍疾病，与大脑相关的疾病和/或慢性疾病具有用处。
• COMPOUNDS HAVING LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISM AND USES THEREOF
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1695955B1

  公开（公告）日：2011-10-12
• US7875745B2
  申请人：——

  公开号：US7875745B2

  公开（公告）日：2011-01-25
• Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia
  作者：Masahiko Terakado、Hidehiro Suzuki、Kazuya Hashimura、Motoyuki Tanaka、Hideyuki Ueda、Keisuke Hirai、Masaki Asada、Masahiro Ikura、Naoki Matsunaga、Hiroshi Saga、Koji Shinozaki、Naoko Karakawa、Yuka Takada、Masashi Minami、Hiromu Egashira、Yoshihiro Sugiura、Masanori Yamada、Shinji Nakade、Yoshikazu Takaoka

  DOI：10.1021/acsmedchemlett.7b00383

  日期：2017.12.14

  Scaffold hopping from the amide group of lead compound ONO 7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA(1)) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPAI receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [H-3]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.