5-phenylnicotinoyl chloride | 1261785-72-1

• 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-phenylnicotinoyl chloride
• 英文别名: 5-Phenylnicotinoyl chloride；5-phenylpyridine-3-carbonyl chloride
• CAS: 1261785-72-1
• 化学式: C₁₂H₈ClNO
• 分子量: 217.655
• InChiKey: JEZYMWUNEYUNFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-phenylnicotinoyl chloride 、 3,4-二氢-1H-喹噁啉-2-酮 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 4-[(5-Phenylpyridin-3-Yl)carbonyl]-3,4-Dihydroquinoxalin-2(1h)-One
  参考文献：
  名称：

  Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design

  摘要：

  Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low mu M level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.107
• 作为产物：
  描述：

  5-溴烟酸 在 potassium phosphate 、 氯化亚砜 、 palladium diacetate 作用下， 以 水 、 异丙醇 为溶剂， 反应 11.0h， 生成 5-phenylnicotinoyl chloride
  参考文献：
  名称：

  Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor

  摘要：

  We introduce the term 'silent agonists' to describe ligands that can place the alpha 7 nicotinic acetylcholine receptor (nAChR) into a desensitized state with little or no apparent activation of the ion channel, forming a complex that can subsequently generate currents when treated with an allosteric modulator. KC-1 (5'-phenylanabaseine) was synthesized and identified as a new silent agonist for the alpha 7 nAChR; it binds to the receptor but does not activate alpha 7 nAChR channel opening when applied alone, and its agonism is revealed by co-application with the type II positive allosteric modulator PNU-120596 in the Xenopus oocyte system. The concise synthesis was accomplished in three steps with the C-C bonds formed via Pd-catalyzed mono-arylation and organolithium coupling with N-Boc piperidinone. Comparative structural analyses indicate that a positive charge, an H-bond acceptor, and an aryl ring in a proper arrangement are needed to constitute one class of silent agonist for the alpha 7 nAChR. Because silent agonists may act on signaling pathways not involving ion channel opening, this class of alpha 7 nAChR ligands may constitute a new alternative for the development of alpha 7 nAChR therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.039

文献信息

• [EN] 2,3-DIHYDRO-4H-BENZO[B][1,4]OXAZIN-4-YL)(5-(PHENYL)-PYRIDIN-3-YL)METHANONE DERIVATIVES AND SIMILAR COMPOUNDS AS CYP11A1 INHIBITORS FOR THE TREATMENT OF PROSTATE CANCER<br/>[FR] DÉRIVÉS DE 2,3-DIHYDRO-4H-BENZO[B][1,4]OXAZIN-4-YL)(5-(PHÉNYL)-PYRIDIN-3-YL)MÉTHANONE ET COMPOSÉS SIMILAIRES SERVANT D'INHIBITEURS DE CYP11A1 POUR LE TRAITEMENT DU CANCER DE LA PROSTATE
  申请人：ORION CORP

  公开号：WO2022117920A1

  公开（公告）日：2022-06-09

  The present invention relates to compounds of formula (I) wherein A is a 3-10 membered carbocyclyl or a 4-12 membered heterocyclyl containing 1-4 heteroatoms selected from O, N or S; B is any of the following groups (1) (2) or (3 ); C is any of the following groups (1') (2') (3") or (4') G1is CH2, NH or O; G2and G3are, independently, is CH or N: Z is -C(O)-, -SO2-, -C1-3alkyl- or -CH2-C(O)-; L is a bond, -C1-7alkyl- or -C1-7alkenyl-; The compounds of formula (I) are cytochrome P450 monooxygenase 11A1 (CYP11A1) inhibitors. The compounds are useful as medicaments in the treatment of steroid receptor, for example androgen receptor or estrogen receptor, dependent diseases and conditions, such as cancer including prostate cancer and estrogen cancer.

  本发明涉及式(I)化合物，其中A是3-10个成员的碳环或4-12个成员的杂环，其中包含1-4个从O、N或S中选择的杂原子；B是以下任意一组(1)、(2)或(3)；C是以下任意一组(1')、(2')、(3")或(4')；G1是CH2、NH或O；G2和G3分别是CH或N；Z是-C(O)-、-SO2-、-C1-3烷基-或-CH2-C(O)-；L是键、-C1-7烷基-或-C1-7烯基-；式(I)化合物是细胞色素P450单加氧酶11A1(CYP11A1)抑制剂。这些化合物在治疗类固醇受体，例如雄激素受体或雌激素受体依赖性疾病和病况，如包括前列腺癌和雌激素癌在内的癌症中，作为药物是有用的。
• C3‐Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity
  作者：Ming Zhang、Qingyang Zhou、Heng Luo、Zi‐Lu Tang、Xiufang Xu、Xiao‐Chen Wang

  DOI：10.1002/anie.202216894

  日期：2023.2

  C3-selective cyanation of pyridines was accomplished by a tandem process of borane-catalyzed pyridine hydroboration, substitution of the resulting dihydropyridine with a cyano electrophile, and finally oxidative aromatization. This method was suitable for use in late-stage cyanation of pyridine drugs.

  吡啶的 C3 选择性氰化是通过硼烷催化的吡啶硼氢化、用氰基亲电试剂取代所得二氢吡啶、最后氧化芳构化的串联过程完成的。该方法适用于吡啶类药物的后期氰化反应。
• Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases
  作者：Lushun Wang、Monica J. Bohmer、Jinhua Wang、Flore Nardella、Jaeson Calla、Mariana Laureano De Souza、Kyra A. Schindler、Lukas Montejo、Nimisha Mittal、Frances Rocamora、Mayland Treat、Jordan T. Charlton、Patrick K. Tumwebaze、Philip J. Rosenthal、Roland A. Cooper、Ratna Chakrabarti、Elizabeth A. Winzeler、Debopam Chakrabarti、Nathanael S. Gray

  DOI：10.1021/acs.jmedchem.3c02046

  日期：2024.1.25

  urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound 1 as a lead antimalarial, which was initially developed to target human

  尽管根除疟疾的努力取得了进展，但该疾病仍然对全球健康构成重大威胁。非洲正在出现对一线治疗的获得性耐药，这迫切需要开发新型抗疟药物。鉴于已批准或正在进行临床试验的多种激酶靶向药物的可用性，重新利用人类激酶抑制剂提供了一条潜在的快速途径。对 II 型人类激酶抑制剂库的表型筛选将化合物1鉴定为一种主要抗疟药，该药物最初是针对人类肝配蛋白 A 型受体 2 (EphA2) 开发的。在这里，我们报告了化合物1的构效关系研究和先导化合物优化，最终得到了具有改善的抗疟活性和选择性的化合物33 。
• Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design
  作者：Bryan C. Duffy、Shuang Liu、Gregory S. Martin、Ruifang Wang、Ming Min Hsia、He Zhao、Cheng Guo、Michael Ellis、John F. Quinn、Olesya A. Kharenko、Karen Norek、Emily M. Gesner、Peter R. Young、Kevin G. McLure、Gregory S. Wagner、Damodharan Lakshminarasimhan、Andre White、Robert K. Suto、Henrik C. Hansen、Douglas B. Kitchen

  DOI：10.1016/j.bmcl.2015.04.107

  日期：2015.7

  Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low mu M level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor
  作者：Kinga Chojnacka、Roger L. Papke、Nicole A. Horenstein

  DOI：10.1016/j.bmcl.2013.05.039

  日期：2013.7

  We introduce the term 'silent agonists' to describe ligands that can place the alpha 7 nicotinic acetylcholine receptor (nAChR) into a desensitized state with little or no apparent activation of the ion channel, forming a complex that can subsequently generate currents when treated with an allosteric modulator. KC-1 (5'-phenylanabaseine) was synthesized and identified as a new silent agonist for the alpha 7 nAChR; it binds to the receptor but does not activate alpha 7 nAChR channel opening when applied alone, and its agonism is revealed by co-application with the type II positive allosteric modulator PNU-120596 in the Xenopus oocyte system. The concise synthesis was accomplished in three steps with the C-C bonds formed via Pd-catalyzed mono-arylation and organolithium coupling with N-Boc piperidinone. Comparative structural analyses indicate that a positive charge, an H-bond acceptor, and an aryl ring in a proper arrangement are needed to constitute one class of silent agonist for the alpha 7 nAChR. Because silent agonists may act on signaling pathways not involving ion channel opening, this class of alpha 7 nAChR ligands may constitute a new alternative for the development of alpha 7 nAChR therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.