4-[2-氨基-5-[4-[((二甲基氨基)甲基]-2-噻吩基]-3-吡啶基]-2-[[((2Z))-4,4,4-三氟-1-甲基-2-丁烯-1-基]氧基]苯甲酰胺 | 1364269-06-6

• 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
• 中文名称: 4-[2-氨基-5-[4-[((二甲基氨基)甲基]-2-噻吩基]-3-吡啶基]-2-[[((2Z))-4,4,4-三氟-1-甲基-2-丁烯-1-基]氧基]苯甲酰胺
• 英文名称: 4-[2-amino-5-[4-[(dimethylamino)methyl]-2-thienyl]-3-pyridinyl]-2-[[(2Z)-4,4,4-trifluoro-1-methyl-2-buten-1-yl]oxy]benzamide
• 英文别名: rac-CCT 250863；(+/-)-(Z)-4-(2-amino-5-(4-((dimethylamino)methyl)thiophen-2-yl)pyridin-3-yl)-2-((5,5,5-trifluoropent-3-en-2-yl)oxy)benzamide；4-[2-amino-5-[4-[(dimethylamino)methyl]thiophen-2-yl]pyridin-3-yl]-2-[(Z)-5,5,5-trifluoropent-3-en-2-yl]oxybenzamide
• CAS: 1364269-06-6
• 化学式: C₂₄H₂₅F₃N₄O₂S
• 分子量: 490.549
• InChiKey: LLEOOSLUHRQCHZ-SREVYHEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-[2-氨基-5-[4-[((二甲基氨基)甲基]-2-噻吩基]-3-吡啶基]-2-[[((2Z))-4,4,4-三氟-1-甲基-2-丁烯-1-基]氧基]苯甲酰胺 在 Chiral HPLC (LUX cellulose II) 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 96.0h， 生成 (R)-(Z)-4-(2-amino-5-(4-((dimethylamino)methyl)thiophen-2-yl)pyridin-3-yl)-2-((5,5,5-trifluoropent-3-en-2-yl)oxy)benzamide 、 (S)-(Z)-4-(2-amino-5-(4-((dimethylamino)methyl)thiophen-2-yl)pyridin-3-yl)-2-((5,5,5-trifluoropent-3-en-2-yl)oxy)benzamide
  参考文献：
  名称：

  Design of Potent and Selective Hybrid Inhibitors of the Mitotic Kinase Nek2: Structure–Activity Relationship, Structural Biology, and Cellular Activity

  摘要：

  We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells.

  DOI：

  10.1021/jm201683b
• 作为产物：
  描述：

  5,5,5-trifluoro-3-pentyn-2-ol 在 偶氮二甲酸二叔丁酯 、 Lindlar's catalyst 、 氨 、 氢气 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 97.5h， 生成 4-[2-氨基-5-[4-[((二甲基氨基)甲基]-2-噻吩基]-3-吡啶基]-2-[[((2Z))-4,4,4-三氟-1-甲基-2-丁烯-1-基]氧基]苯甲酰胺
  参考文献：
  名称：

  Design of Potent and Selective Hybrid Inhibitors of the Mitotic Kinase Nek2: Structure–Activity Relationship, Structural Biology, and Cellular Activity

  摘要：

  We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells.

  DOI：

  10.1021/jm201683b

文献信息

• SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
  申请人：Celgene Corporation

  公开号：US20210113576A1

  公开（公告）日：2021-04-22

  Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

  本文提供了使用(S)-2-(2,6-二酮哌啶-3-基)-4-((2-氟-4-((3-吗啡基氮杂环丙烷-1-基)甲基)苯甲基)氨基)异吲哚啉-1,3-二酮或其对映体、对映体混合物、互变异构体、同位素拓扑异构体或其药学上可接受的盐，与第二种活性剂联合治疗、预防或管理血液恶性肿瘤的方法。第二种活性剂是HDAC抑制剂、BCL2抑制剂、BTK抑制剂、mTOR抑制剂、PI3K抑制剂、PKCβ抑制剂、SYK抑制剂、JAK2抑制剂、极化分裂素激酶抑制剂、EZH2抑制剂、BET抑制剂、去甲基化剂、DOT1L抑制剂、HAT抑制剂、WDR5抑制剂、DNMT1抑制剂、LSD-1抑制剂、G9A抑制剂、PRMT5抑制剂、BRD抑制剂、SUV420H1/H2抑制剂、CARM1抑制剂、PLK1抑制剂、NEK2抑制剂、MEK抑制剂、PHF19抑制剂、PIM抑制剂、IGF-1R抑制剂、XPO1抑制剂、BIRC5抑制剂或化疗药物之一。
• Halogen-containing metathesis catalysts and methods thereof
  申请人：Massachusetts Institute of Technology

  公开号：US11020730B2

  公开（公告）日：2021-06-01

  The present disclosure provides compounds, compositions, and methods for preparing alkenyl halides and/or haloalkyl-substituted olefins with Z-selectivity. The methods are particularly useful for preparing alkenyl fluorides such as CF3-substituted olefins by means of cross-metathesis reactions using halogen-containing molybdenum and tungsten complexes.

  本公开提供了用于制备具有 Z 选择性的烯基卤化物和/或卤代烷基取代烯烃的化合物、组合物和方法。这些方法尤其适用于通过使用含卤素的钼和钨络合物进行交叉嵌合反应制备烯基氟化物，如 CF3 取代的烯烃。
• HALOGEN-CONTAINING METATHESIS CATALYSTS AND METHODS THEREOF
  申请人：Massachusetts Institute of Technology

  公开号：US20190314799A1

  公开（公告）日：2019-10-17

  The present disclosure provides compounds, compositions, and methods for preparing alkenyl halides and/or haloalkyl-substituted olefins with Z-selectivity. The methods are particularly useful for preparing alkenyl fluorides such as CF 3 -substituted olefins by means of cross-metathesis reactions using halogen-containing molybdenum and tungsten complexes.
• [EN] SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE<br/>[FR] COMPOSÉS DE 4-AMINOISOINDOLINE -1,3-DIONE SUBSTITUÉS ET SECONDS AGENTS ACTIFS À USAGE COMBINÉ
  申请人：CELGENE CORP

  公开号：WO2021080955A1

  公开（公告）日：2021-04-29

  Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3- morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.
• [EN] METHODS FOR TREATING CANCER WITH COMBINATION THERAPIES<br/>[FR] MÉTHODES POUR TRAITER UN CANCER AVEC DES POLYTHÉRAPIES
  申请人：CELGENE CORP

  公开号：WO2021262962A1

  公开（公告）日：2021-12-30

  Provided herein are methods of using a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof), in combination with a second active agent for treating cancer. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, an NEK2 inhibitor, an AURKB inhibitor, an MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPOl inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRC5 inhibitor, or a DNA methyltransferase inhibitor.