6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide | 1024604-99-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide
• 英文别名: 6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridine-3-ylethyl)amide；6-chloro-N-(2-hydroxy-2-(pyridin-3-yl)ethyl)pyridazine-3-carboxamide；6-chloro-N-(2-hydroxy-2-pyridin-3-ylethyl)pyridazine-3-carboxamide
• CAS: 1024604-99-6
• 化学式: C₁₂H₁₁ClN₄O₂
• 分子量: 278.698
• InChiKey: DLTVTTAJIDHOAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide 、 5-trifluoromethyl-3,4-dihydro-1'H-spiro(chromene-2,4'-piperidine)-1'-carboxylate hydrochloride 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 48.0h， 以49%的产率得到N-(2-hydroxy-2-pyridin-3-ylethyl)-6-[5-(trifluoromethyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]pyridazine-3-carboxamide
  参考文献：
  名称：

  Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]

  摘要：

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.043
• 作为产物：
  描述：

  6-羟基-3-哒嗪甲酸 、 2-amino-1-(pyridin-3-yl)ethanol dihydrochloride 在 氯化亚砜 、 N,N-二甲基甲酰胺 、 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以22%的产率得到6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide
  参考文献：
  名称：

  Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats

  摘要：

  Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.101

文献信息

• Discovery of novel SCD1 inhibitors: 5-Alkyl-4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4′-piperidine] analogs
  作者：Yoshikazu Uto、Yuko Ueno、Yohei Kiyotsuka、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Toshiyuki Takagi、Satoko Wakimoto、Jun Ohsumi

  DOI：10.1016/j.ejmech.2011.02.002

  日期：2011.5

  Expansion of the 6-membered ring and subsequent fine-tuning of the newly obtained 7-membered spiropiperidine structure resulted in the discovery of a series of novel and potent SCD1 inhibitors. Preliminary SAR was explored by modifying an alkyl chain on the azepine nitrogen and resulted in the identification of a highly potent SCD1 inhibitor: 6-[5-(cyclopropylmethyl)-4,5-dihydro-1'H,3H-spiro[1,5-benzoxazepine-2,4'-piperidin]-1'-yl]-N-(2-hydroxy-2-pyridin-3-ylethyl)pyridazine-3-carboxamide (9). Compound 9 exhibited an IC50 value of 0.01 mu M against human SCD1. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]
  作者：Yoshikazu Uto、Yohei Kiyotsuka、Yuko Ueno、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Tsuneo Deguchi、Makiko Yamada、Nobuaki Watanabe、Masahiro Konishi、Nobuya Kurikawa、Toshiyuki Takagi、Satoko Wakimoto、Keita Kono、Jun Ohsumi

  DOI：10.1016/j.bmcl.2009.11.043

  日期：2010.1

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.
• Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats
  作者：Yoshikazu Uto、Tsuneaki Ogata、Yohei Kiyotsuka、Yuko Ueno、Yuriko Miyazawa、Hitoshi Kurata、Tsuneo Deguchi、Nobuaki Watanabe、Masahiro Konishi、Ryo Okuyama、Nobuya Kurikawa、Toshiyuki Takagi、Satoko Wakimoto、Jun Ohsumi

  DOI：10.1016/j.bmcl.2009.10.101

  日期：2010.1

  Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd). (C) 2009 Elsevier Ltd. All rights reserved.