2-异丙基-2H-1,2,3-三唑-4-胺 | 959237-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 中文名称: 2-异丙基-2H-1,2,3-三唑-4-胺
• 英文名称: 2-isopropyl-2H-1,2,3-triazol-4-amine
• 英文别名: 2-propan-2-yltriazol-4-amine
• CAS: 959237-97-9
• 化学式: C₅H₁₀N₄
• mdl: MFCD09864368
• 分子量: 126.161
• InChiKey: JMKNFBHEYCDIRE-UHFFFAOYSA-N

物化性质

• 沸点：
  259.0±32.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-异丙基-2H-1,2,3-三唑-4-胺 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3

  摘要：

  Inhibition of triacylglycerol (TAG) biosynthetic enzymes has been suggested as a promising strategy to treat insulin resistance, diabetes, dyslipidemia, and hepatic steatosis. Monoacylglycerol acyltransferase 3 (MGAT3) is an integral membrane enzyme that catalyzes the acylation of both monoacylglycerol (MAG) and diacylglycerol (DAG) to generate DAG and TAG, respectively. Herein, we report the discovery and characterization of the first selective small molecule inhibitors of MGAT3. Isoindoline-5-sulfonamide (6f, PF-06471553) selectively inhibits MGAT3 with high in vitro potency and cell efficacy. Because the gene encoding MGAT3 (MOGAT3) is found only in higher mammals and humans, but not in rodents, a transgenic mouse model expressing the complete human MOGAT3 was used to characterize the effects of 6f in vivo. In the presence of a combination of diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2) inhibitors, an oral administration of 6f exhibited inhibition of the incorporation of deuterium-labeled glycerol into TAG in this mouse model. The availability of a potent and selective chemical tool and a humanized mouse model described in this report should facilitate further dissection of the physiological function of MGAT3 and its role in lipid homeostasis.

  DOI：

  10.1021/acs.jmedchem.5b01008

文献信息

• A Modular and Diastereoselective 5 + 1 Cyclization Approach to N-(Hetero)Aryl Piperidines
  作者：Matthew A. Larsen、Elisabeth T. Hennessy、Madeleine C. Deem、Yu-hong Lam、Josep Saurí、Aaron C. Sather

  DOI：10.1021/jacs.9b13114

  日期：2020.1.15

  A new general de novo synthesis of pharmaceutically important N-(hetero)aryl piperidines is reported. This protocol uses a robustly diastereoselective reductive amination/aza-Michael reaction se-quence to achieve rapid construction of complex polysubstituted ring systems starting from widely available heterocyclic amine nu-cleophiles and carbonyl electrophiles. Notably, the diastereoselec-tivity of

  报道了药学上重要的 N-（杂）芳基哌啶的一种新的通用从头合成。该协议使用稳健的非对映选择性还原胺化/氮杂-迈克尔反应序列，以从广泛可用的杂环胺亲核试剂和羰基亲电试剂开始，快速构建复杂的多取代环系统。值得注意的是，该过程的非对映选择性因水的存在而增强，并且 DFT 计算支持立体化学模型，该模型涉及水配位烯醇中间体的面部选择性质子化。
• [EN] PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF<br/>[FR] COMPOSÉS DE PYRROLOPYRIMIDINE, LEUR UTILISATION À TITRE D'INHIBITEURS DE LA KINASE LRRK2, ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：SOUTHERN RES INST

  公开号：WO2017106771A1

  公开（公告）日：2017-06-22

  The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开涉及某些吡咯吡嘧啶化合物，这些化合物能够抑制某些蛋白激酶，尤其是富含亮氨酸重复激酶2（LRRK2）蛋白。本公开的化合物可用于治疗由或与异常LRRK2激酶活性相关的多种疾病。本公开的化合物可用于治疗包括帕金森病在内的神经退行性疾病；癌前病变和癌症；自身免疫性疾病，如克罗恩病、类风湿关节炎和牛皮癣；以及麻风病（汉森病）。本摘要旨在作为特定领域搜索的扫描工具，并不旨在限制本发明。
• Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3
  作者：Kim Huard、Allyn T. Londregan、Gregory Tesz、Kevin B. Bahnck、Thomas V. Magee、David Hepworth、Jana Polivkova、Steven B. Coffey、Brandon A. Pabst、James R. Gosset、Anu Nigam、Kou Kou、Hao Sun、Kyuha Lee、Michael Herr、Markus Boehm、Philip A. Carpino、Bryan Goodwin、Christian Perreault、Qifang Li、Csilla C. Jorgensen、George T. Tkalcevic、Timothy A. Subashi、Kay Ahn

  DOI：10.1021/acs.jmedchem.5b01008

  日期：2015.9.24

  Inhibition of triacylglycerol (TAG) biosynthetic enzymes has been suggested as a promising strategy to treat insulin resistance, diabetes, dyslipidemia, and hepatic steatosis. Monoacylglycerol acyltransferase 3 (MGAT3) is an integral membrane enzyme that catalyzes the acylation of both monoacylglycerol (MAG) and diacylglycerol (DAG) to generate DAG and TAG, respectively. Herein, we report the discovery and characterization of the first selective small molecule inhibitors of MGAT3. Isoindoline-5-sulfonamide (6f, PF-06471553) selectively inhibits MGAT3 with high in vitro potency and cell efficacy. Because the gene encoding MGAT3 (MOGAT3) is found only in higher mammals and humans, but not in rodents, a transgenic mouse model expressing the complete human MOGAT3 was used to characterize the effects of 6f in vivo. In the presence of a combination of diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2) inhibitors, an oral administration of 6f exhibited inhibition of the incorporation of deuterium-labeled glycerol into TAG in this mouse model. The availability of a potent and selective chemical tool and a humanized mouse model described in this report should facilitate further dissection of the physiological function of MGAT3 and its role in lipid homeostasis.