tert-butyl 2-[(9S)-4,5,13-trimethyl-7-(4-methylphenyl)-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: tert-butyl 2-[(9S)-4,5,13-trimethyl-7-(4-methylphenyl)-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate
• 化学式: C₂₄H₂₈N₄O₂S
• 分子量: 436.6
• InChiKey: NEOVTYQDNTUFDO-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  6

文献信息

• [EN] TERT-BUTYL (S)-2-(4-(PHENYL)-6H-THIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A] [1,4]DIAZEPIN-6-YL) ACETATE DERIVATIVES AND RELATED COMPOUNDS AS BROMODOMAIN BRD4 INHIBITORS FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE TERT-BUTYL (S)-2-(4-(PHÉNYL)-6H-THIÉNO[3,2-F][1,2,4]TRIAZOLO[4,3-A] [1,4]DIAZÉPIN-6-YL) ACÉTATE ET COMPOSÉS APPARENTÉS UTILISÉS EN TANT QU'INHIBITEURS DE BROMODOMAINE BROMOD4 POUR LE TRAITEMENT DU CANCER
  申请人：GENENTECH INC

  公开号：WO2020055976A1

  公开（公告）日：2020-03-19

  The present disclosure relates to te rt-butyl (S)-2-(4-(phenyl)-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl) acetate derivatives and related compounds as bromodomain BRD4 inhibitors for treating cancer. Exemplary compounds are e.g. tert-butyl (S)-2-(4-(4-(3-aminoprop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 1, compound la), tert-butyl(S,E)-2-(4-(4-(3-aminoprop-l-en-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 6, compound 6a) or tert-butyl(S)-2-(4-(4-(3-(hydroxyamino)prop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl)acetate (example 8, compound 8a).Results of biological assays, such as e.g. BRD4 BD1 and BD2 binding (table 2), cell proliferation assays (table 6) and inhibition of MYC expression in MV-4-11 cells (table 7) are disclosed.

  本公开涉及对叔丁基(S)-2-(4-(苯基)-6H-噻吩[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂蒽啉-6-基)醋酸酯衍生物及相关化合物作为治疗癌症的溴结构域BRD4抑制剂。示例化合物包括叔丁基(S)-2-(4-(4-(3-氨基丙-1-炔-1-基)苯基)-2,3,9-三甲基-6H-噻吩[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂蒽啉-6-基)醋酸酯（示例1，化合物la）、叔丁基(S,E)-2-(4-(4-(3-氨基丙-1-烯-1-基)苯基)-2,3,9-三甲基-6H-噻吩[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂蒽啉-6-基)醋酸酯（示例6，化合物6a）或叔丁基(S)-2-(4-(4-(3-(羟胺基)丙-1-炔-1-基)苯基)-2,3,9-三甲基-6H-噻吩[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂蒽啉-6-基)醋酸酯（示例8，化合物8a）。公开了生物测定的结果，例如BRD4 BD1和BD2结合（表2）、细胞增殖测定（表6）以及在MV-4-11细胞中MYC表达的抑制（表7）。
• BROMODOMAIN LIGANDS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
  申请人：Coferon, Inc.

  公开号：US20140243286A1

  公开（公告）日：2014-08-28

  Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

  本文介绍了一种单体，当在水介质中与一个、两个、三个或更多其他单体接触时，能够形成生物上有用的多聚体。在其中一方面，这种单体可以在水介质中（例如在体内）与另一个单体结合形成多聚体（例如二聚体）。考虑到的单体可能包括配体基团、连接元素和连接配体基团和连接元素的连接元素。在水介质中，这些考虑到的单体可以通过每个连接元素连接在一起，因此可以同时调节一个或多个生物分子，例如调节蛋白质或不同蛋白质上的两个或更多结合结构域。
• BIOORTHOGONAL MONOMERS CAPABLE OF DIMERIZING AND TARGETING BROMODOMAINS, AND METHODS OF USING SAME
  申请人：Coferon, Inc.

  公开号：US20140243321A1

  公开（公告）日：2014-08-28

  Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

  本文描述了一种单体，当与一个、两个、三个或更多其他单体在水介质中接触时，能够形成生物上有用的多聚体。在一个方面，这样的单体可以在水介质中（例如在体内）与另一个单体结合形成多聚体（例如二聚体）。考虑到的单体可能包括配体基团、连接元素和连接配体基团和连接元素的连接器元素。在水介质中，这些考虑到的单体可以通过每个连接元素连接在一起，因此可以同时调节一个或多个生物分子，例如调节蛋白质或不同蛋白质上的两个或更多结合域。
• BIVALENT BROMODOMAIN LIGANDS, AND METHODS OF USING SAME
  申请人：Coferon, Inc.

  公开号：US20140243322A1

  公开（公告）日：2014-08-28

  Described herein are compounds capable of modulating one or more biomolecules substantially simultaneously, e.g., modulating two or more binding domains (e.g., bromodomains) on a protein or on different proteins.

  本文描述了一些化合物，能够在实质上同时调节一个或多个生物分子，例如，在蛋白质上或不同蛋白质上调节两个或更多结合域（例如溴结构域）。
• THERAPEUTIC COMPOUNDS AND USES THEREOF
  申请人：Constellation Pharmaceuticals, Inc.

  公开号：US20160158207A1

  公开（公告）日：2016-06-09

  The present invention relates to compounds of formula (I) or formula (II): and to salts thereof, wherein R 1 -R 4 of formula (I) and R 1 -R 3 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

  本发明涉及公式（I）或公式（II）的化合物及其盐，其中公式（I）的R1-R4和公式（II）的R1-R3具有以下定义的任何值，以及其组合物和用途。这些化合物可用作CBP和/或EP300的抑制剂。还包括含有公式（I）或公式（II）的化合物或其药学上可接受的盐的制药组合物，以及使用这些化合物和盐治疗各种CBP和/或EP300介导的疾病的方法。