5-isobutyl-nicotinonitrile | 1585182-42-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-isobutyl-nicotinonitrile
• 英文别名: 5-(2-Methylpropyl)pyridine-3-carbonitrile
• CAS: 1585182-42-8
• 化学式: C₁₀H₁₂N₂
• 分子量: 160.219
• InChiKey: RPIPGENOXHUEKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-isobutyl-nicotinonitrile 在 水 作用下， 以 甲醇 为溶剂， 反应 4.5h， 以82%的产率得到5-isobutyl-nicotinamide
  参考文献：
  名称：

  Engineering the Substrate Specificity of ADP-Ribosyltransferases for Identifying Direct Protein Targets

  摘要：

  Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function in both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids of target proteins. The functional redundancy and overlapping target specificities among the 17 ARTDs in humans make the identification of direct targets of individual ARTD family members in a cellular context a formidable challenge. Here we describe the rational design of orthogonal NAD(+) analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. Guided by initial inhibitor studies with nicotinamide analogues containing substituents at the C-5 position, we synthesized an orthogonal NAD(+) variant and found that it is used as a substrate for several engineered ARTDs (ARTD1, -2, and -6) but not their wild-type counterparts. Comparing the target profiles of ARTD1 (PARP1) and ARTD2 (PARP2) in nuclear extracts highlighted the semi-complementary, yet distinct, protein targeting. Using affinity purification followed by tandem mass spectrometry, we identified 42 direct ARTD1 targets and 301 direct ARTD2 targets. This represents a powerful new technique for identifying direct protein targets of individual ARTD family members, which will facilitate studies delineating the pathway from ARTD activation to a given cellular response.

  DOI：

  10.1021/ja412897a
• 作为产物：
  描述：

  5-溴烟腈 、 2-methylpropyl zinc bromide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 作用下， 以 四氢呋喃 为溶剂， 以41%的产率得到5-isobutyl-nicotinonitrile
  参考文献：
  名称：

  Engineering the Substrate Specificity of ADP-Ribosyltransferases for Identifying Direct Protein Targets

  摘要：

  Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function in both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids of target proteins. The functional redundancy and overlapping target specificities among the 17 ARTDs in humans make the identification of direct targets of individual ARTD family members in a cellular context a formidable challenge. Here we describe the rational design of orthogonal NAD(+) analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. Guided by initial inhibitor studies with nicotinamide analogues containing substituents at the C-5 position, we synthesized an orthogonal NAD(+) variant and found that it is used as a substrate for several engineered ARTDs (ARTD1, -2, and -6) but not their wild-type counterparts. Comparing the target profiles of ARTD1 (PARP1) and ARTD2 (PARP2) in nuclear extracts highlighted the semi-complementary, yet distinct, protein targeting. Using affinity purification followed by tandem mass spectrometry, we identified 42 direct ARTD1 targets and 301 direct ARTD2 targets. This represents a powerful new technique for identifying direct protein targets of individual ARTD family members, which will facilitate studies delineating the pathway from ARTD activation to a given cellular response.

  DOI：

  10.1021/ja412897a

文献信息

• DERIVATIVES OF 2-PYRIDIN-2-YL-PYRAZOL-3(2H)-ONE, PREPARATION AND THERAPEUTIC USE THEREOF AS HIF ACTIVATORS
  申请人：ALTENBURGER Jean-Michel

  公开号：US20110294788A1

  公开（公告）日：2011-12-01

  The present invention relates to novel substituted dihydropyrazolone derivatives, to their preparation and to their therapeutic use as activators of the transcription factor HIF.

  本发明涉及新型取代二氢吡唑酮衍生物，其制备以及作为转录因子HIF激活剂的治疗用途。
• [EN] COMPOUNDS AND METHODS FOR MODULATING ADENOSINE A2B RECEPTOR AND ADENOSINE A2A RECEPTOR<br/>[FR] COMPOSÉS ET PROCÉDÉS DE MODULATION DU RÉCEPTEUR A2B DE L'ADÉNOSINE ET DU RÉCEPTEUR A2A DE L'ADÉNOSINE
  申请人：CORVUS PHARMACEUTICALS INC

  公开号：WO2019046784A1

  公开（公告）日：2019-03-07

  Disclosed herein, inter alia, are compositions and methods for modulating Adenosine Receptors. In an aspect is provided a method of inhibiting Adenosine A2B Receptor activity and Adenosine A2A Receptor activity, the method including contacting the Adenosine A2B Receptor and Adenosine A2A Receptor with a compound as described herein, including embodiments.

  在此披露的内容包括调节腺苷受体的组合物和方法。在一个方面，提供了一种抑制腺苷A2B受体活性和腺苷A2A受体活性的方法，该方法包括将腺苷A2B受体和腺苷A2A受体与本文描述的化合物接触，包括各种实施方式。
• IMMUNOMODULATOR COMPOUNDS
  申请人：CHEMOCENTRYX, INC.

  公开号：US20180008554A1

  公开（公告）日：2018-01-11

  Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R 1 , R 2a , R 2b , R 2c , R 3 , R 4 , R 5 , R 6a , R 6b , m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  提供了一些有用的免疫调节剂。这些化合物具有以下式（II）：包括其立体异构体和药用盐，其中R1、R2a、R2b、R2c、R3、R4、R5、R6a、R6b、m和n的定义如本文所述。还公开了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• [EN] BENZYLAMINE DERIVATIVE, PREPARATION METHOD THEREFOR AND USE THEREOF<br/>[FR] DÉRIVÉ DE BENZYLAMINE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 苄胺类衍生物及其制备方法与用途
  申请人：ACAD OF MILITARY MEDICAL SCIENCES

  公开号：WO2022033303A1

  公开（公告）日：2022-02-17

  涉及苄胺类衍生物及其制备方法与用途。具体涉及通式(Ⅰ)所示的苄胺类衍生物，或其药学上可接受的立体异构体、盐、溶剂化物或前药，其与人PD-L1有很强的结合能力，能明显抑制PD-1/PD-L1相互作用，具有显著地体内抗肿瘤药效。因此，还涉及所述苄胺类衍生物的制备方法及其在制备治疗与PD-1/PD-L1相关疾病的药物中的用途，
• Immunomodulator compounds
  申请人：CHEMOCENTRYX, INC.

  公开号：US10639284B2

  公开（公告）日：2020-05-05

  Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2a, R2b, R2c, R3, R4, R5, R6a, R6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  本研究提供了可用作免疫调节剂的化合物。这些化合物具有下式（II）： 其中 R1、R2a、R2b、R2c、R3、R4、R5、R6a、R6b、m 和 n 如本文所定义。此外，还公开了与制备和使用此类化合物相关的方法，以及包含此类化合物的药物组合物。