N¹-(4-cyanophenyl)-N⁵-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N¹-(4-cyanophenyl)-N⁵-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide
• 英文别名: N-(4-cyanophenyl)-N'-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide；N-(4-cyanophenyl)-N'-(9-ethylcarbazol-3-yl)-3-methylpentanediamide
• 化学式: C₂₇H₂₆N₄O₂
• 分子量: 438.529
• InChiKey: JQVHQIWDFKPLBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  86.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(4-cyanophenyl)-N⁵-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 14.0h， 以14.43%的产率得到N¹-(4-cyanophenyl)-N⁵-(9-ethyl-9H-carbazol-3-yl)-N',N⁵,3-trimethylpentanediamide
  参考文献：
  名称：

  CONDENSED HETEROCYCLIC COMPOUND

  摘要：

  公开号：

  EP2759533B1

文献信息

• Identification of novel quinazolinedione derivatives as RORγt inverse agonist
  作者：Yoshiyuki Fukase、Ayumu Sato、Yoshihide Tomata、Atsuko Ochida、Mitsunori Kono、Kazuko Yonemori、Keiko Koga、Toshitake Okui、Masashi Yamasaki、Yasushi Fujitani、Hideyuki Nakagawa、Ryoukichi Koyama、Masaharu Nakayama、Robert Skene、Bi-Ching Sang、Isaac Hoffman、Junya Shirai、Satoshi Yamamoto

  DOI：10.1016/j.bmc.2017.12.039

  日期：2018.2

  Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was also optimized; a quinazolinedione derivative 18i suppressed the increase of IL-17A mRNA level in the lymph node of a rat model of experimental autoimmune encephalomyelitis (EAE) upon oral administration. These results indicate that the novel quinazolinedione derivatives have great potential as orally available small-molecule ROR gamma t inverse agonists for the treatment of Th17-driven autoimmune diseases. A U-shaped bioactive conformation of this chemotype with ROR gamma t protein was also observed. (C) 2017 Elsevier Ltd. All rights reserved.
• ROR GAMMA T INHIBITORS AND TOPICAL USES THEREOF
  申请人：Dermira, Inc

  公开号：EP4054712A2

  公开（公告）日：2022-09-14
• ROR Gamma T Inhibitors and Topical Uses Thereof
  申请人：Dermira, inc.

  公开号：US20220409643A1

  公开（公告）日：2022-12-29

  The present disclosure is directed to use of RORγt inhibitors in the treatment of autoimmune disorders, e.g., autoimmune disorders of the skin. This disclosure is also directed to pharmaceutical compositions comprising an RORγt inhibitor and a pharmaceutically acceptable carrier for topical administration.
• US9120776B2
  申请人：——

  公开号：US9120776B2

  公开（公告）日：2015-09-01
• [EN] CONDENSED HETEROCYCLIC COMPOUND<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE CONDENSÉ
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013042782A1

  公开（公告）日：2013-03-28

  　ＲＯＲγｔ阻害作用を有する縮合複素環化合物を提供すること。式（Ｉ'）：〔式中、各記号は本明細書中で定義した通りである。〕で表される化合物（但し、２－（２－（（４－シアノフェニル）アミノ）－２－オキソエトキシ）－Ｎ－（９－エチル－９Ｈ－カルバゾール－３－イル）アセトアミドおよびＮ－（４－シアノフェニル）－Ｎ'－（９－エチル－９Ｈ－カルバゾール－３－イル）－３－メチルペンタンジアミドは除く。）またはその塩。