1-(1,3-dihydro-2H-isoindol-2-yl)-2,2,2-trifluoroethanone | 832-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-(1,3-dihydro-2H-isoindol-2-yl)-2,2,2-trifluoroethanone
• 英文别名: 2,2,2-trifluoro-1-(isoindolin-2-yl)ethanone；2-trifluoroacetyl-1,3-dihydro-isoindole；2-trifluoroacetyl-isoindoline；2-Trifluoracetyl-isoindolin；1-(1,3-dihydro-isoindol-2-yl)-2,2,2-trifluoro-ethanone；1-(1,3-dihydroisoindol-2-yl)-2,2,2-trifluoroethanone
• CAS: 832-51-9
• 化学式: C₁₀H₈F₃NO
• 分子量: 215.175
• InChiKey: OGPIVYSQASVHRE-UHFFFAOYSA-N

物化性质

• 沸点：
  332.1±42.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(1,3-dihydro-2H-isoindol-2-yl)-2,2,2-trifluoroethanone 在 氯磺酸 、 copper(l) iodide 、 (±)-N,N-dimethyl-trans-1,2-diaminocyclohexane 、 氨 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-(2-(3,3-difluorocyclobutyl)-2H-1,2,3-triazol-4-yl)-2-(2-(3-methoxyphenyl)acetyl)isoindoline-5-sulfonamide
  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
• 作为产物：
  描述：

  2-(甲苯-4-磺酰基)-2,3-二氢-1H-异吲哚 在 乙醚 、 氢溴酸 、 丙酸 、 苯酚 作用下， 生成 1-(1,3-dihydro-2H-isoindol-2-yl)-2,2,2-trifluoroethanone
  参考文献：
  名称：

  Notes - Facile Synthesis of Dihydroisoindole

  摘要：

  DOI：

  10.1021/jo01361a603

文献信息

• [EN] HETEROARYL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEURS UTILISATIONS
  申请人：CELGENE AVILOMICS RES INC

  公开号：WO2016090079A1

  公开（公告）日：2016-06-09

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are effective as inhibitors of one or more protein kinases. Such compounds have general formula I or a pharmaceutically acceptable salt thereof, wherein Ring A, Ring B, W, Ry, R3 and R4 are as defined herein.

  本发明提供了化合物、其药学上可接受的组合物，以及使用它们的方法。现在已经发现，本发明的化合物及其药学上可接受的组合物作为一种或多种蛋白激酶的抑制剂是有效的。这些化合物具有通式I或其药学上可接受的盐，其中环A、环B、W、Ry、R3和R4如本文所定义。
• Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 2: Isoindoline containing inhibitors
  作者：Sebastiaan Van Goethem、Pieter Van der Veken、Véronique Dubois、Anna Soroka、Anne-Marie Lambeir、Xin Chen、Achiel Haemers、Simon Scharpé、Ingrid De Meester、Koen Augustyns

  DOI：10.1016/j.bmcl.2008.05.079

  日期：2008.7

  selective and potent inhibitors of dipeptidyl peptidases 8 and 9, we synthesized a series of substituted isoindolines as modified analogs of allo-Ile-isoindoline, the reference DPP8/9 inhibitor. The influence of phenyl substituents and different P2 residues on the inhibitors' affinity toward other DPPs and more specifically, their potential to discriminate between DPP8 and DPP9 will be discussed. Within

  为了获得二肽基肽酶8和9的选择性有效抑制剂，我们合成了一系列取代的异吲哚啉作为参考DPP8 / 9抑制剂allo-Ile-isoindoline的修饰类似物。将讨论苯基取代基和不同的P2残基对抑制剂对其他DPP亲和力的影响，更具体地说，是它们在DPP8和DPP9之间区分的潜力。在该系列中，化合物8j被证明是对DPP II的活性低的DPP8 / 9的有效和选择性抑制剂。
• NEW PYRIDONE DERIVATES WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
  申请人：Stenkamp Dirk

  公开号：US20080255083A1

  公开（公告）日：2008-10-16

  The present invention relates to compounds of general formula I wherein the groups and radicals B, k, L, U, V, W, X, Y, Z, R 1 , R 2 , have the meanings given in claim 1 . Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及一般式I的化合物，其中B、k、L、U、V、W、X、Y、Z、R1、R2的基团和基团具有权利要求1中所给出的含义。此外，本发明涉及含有至少一种根据本发明的化合物的制药组合物。由于它们的MCH受体拮抗活性，本发明的制药组合物适用于治疗代谢障碍和/或进食障碍，特别是肥胖症、暴食症、厌食症、过度进食和糖尿病。
• Pyridone derivates with MCH antagonistic activity and medicaments comprising these compounds
  申请人：Boehringer Ingelheim International GmbH

  公开号：US08067590B2

  公开（公告）日：2011-11-29

  The present invention relates to compounds of general formula I wherein the groups and radicals B, k, L, U, V, W, X, Y, Z, R1, R2, have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及通式I的化合物，其中B、k、L、U、V、W、X、Y、Z、R1、R2的基团和基团具有权利要求1所给出的含义。此外，本发明涉及含有至少一种根据本发明的化合物的制药组合物。由于它们的MCH受体拮抗活性，根据本发明的制药组合物适用于治疗代谢紊乱和/或进食障碍，特别是肥胖症、暴食症、厌食症、过度进食和糖尿病。
• Nitrogen-containing condensed heterocyclic compound
  申请人：Busujima Tsuyoshi

  公开号：US09035059B2

  公开（公告）日：2015-05-19

  There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group, RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula —CR11R12—, —CO—, —CO—O—, or —CO—NH—, W represents a single bond or a C1-3 alkylene group, and Ring B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group, Y represents a nitrogen atom or the formula N+(RF), RF represents a C1-4 alkyl group, and m and n, which may be the same or different, each represent an integer of 0 or 1.

  提供以下通式（I）表示的化合物或其药学上可接受的盐，具有优越的单酰基甘油酰基转移酶2抑制作用：其中，环A代表部分饱和的杂环基，芳基或杂芳基，RB代表C4-18烷基，C3-8环烷基，部分饱和的芳基，芳基或以下式（II）：其中，V代表式—CR11R12—，—CO—，—CO—O—或—CO—NH—，W代表单键或C1-3烷基，环B代表C3-8环烷基，C3-8环烯基，部分饱和的杂环基，饱和杂环基，芳基或杂芳基，Y代表氮原子或式N+（RF），RF代表C1-4烷基，m和n分别表示0或1，可以相同也可以不同。