7-chloro-5-(methylsulfonyl)-2,3-dihydro-1H-indole hydrochloride | 1263281-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 7-chloro-5-(methylsulfonyl)-2,3-dihydro-1H-indole hydrochloride
• 英文别名: 7-chloro-5-methylsulfonyl-2,3-dihydro-1H-indole;hydrochloride
• CAS: 1263281-90-8
• 化学式: C₉H₁₀ClNO₂S*ClH
• 分子量: 268.164
• InChiKey: PYXFKXIRNKQLGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三光气 、 7-chloro-5-(methylsulfonyl)-2,3-dihydro-1H-indole hydrochloride 、 N-Boc-4-哌啶乙醇 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 四氢呋喃 为溶剂， 反应 19.0h， 以55%的产率得到2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl 7-chloro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate
  参考文献：
  名称：

  Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists

  摘要：

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.028
• 作为产物：
  描述：

  7-氯吲哚 在 盐酸 、 溴 、 potassium thioacyanate 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 7-chloro-5-(methylsulfonyl)-2,3-dihydro-1H-indole hydrochloride
  参考文献：
  名称：

  Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists

  摘要：

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.028

文献信息

• Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists
  作者：Kenjiro Sato、Hiromichi Sugimoto、Kentaro Rikimaru、Hiroshi Imoto、Masahiro Kamaura、Nobuyuki Negoro、Yoshiyuki Tsujihata、Hirohisa Miyashita、Tomoyuki Odani、Toshiki Murata

  DOI：10.1016/j.bmc.2014.01.028

  日期：2014.3

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-(1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.