tert-butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate | 1268520-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡唑类
• 英文名称: tert-butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate
• 英文别名: 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylic acid tert-butyl ester；tert-Butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate；tert-butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carboxylate
• CAS: 1268520-16-6
• 化学式: C₁₁H₁₇N₃O₂
• 分子量: 223.275
• InChiKey: KGBHFJOKPVPTJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate 在 三氟乙酸 作用下， 反应 12.0h， 生成 1,4,5,6-四氢-1-甲基吡咯并[3,4-C]吡唑
  参考文献：
  名称：

  [EN] PYRIMIDOPYRAZINE COMPOUND AND USE THEREOF
  [FR] COMPOSÉ DE PYRIMIDOPYRAZINE ET SON UTILISATION
  [ZH] 嘧啶并吡嗪酮化合物及其用途

  摘要：

  一种有效抑制MAT2A的新化合物，其为式III所示化合物，或者式III所示化合物的互变异构体、立体异构体、水合物、溶剂化物、药学可接受的盐或前药：其中，L1选自-O-、-S-、-N(RL1)-和单键；RL1选自氢和C1-C6烷基；R1、R2、R3、R4的定义如说明书中所述；所述化合物能够有效抑制MAT2A酶活性，具有广阔的应用前景。

  公开号：

  WO2022206730A1
• 作为产物：
  描述：

  1-叔丁氧碳基-3-吡咯烷酮 以 四氢呋喃 、 乙醇 为溶剂， 反应 33.0h， 生成 tert-butyl 1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate
  参考文献：
  名称：

  [EN] PYRIMIDOPYRAZINE COMPOUND AND USE THEREOF
  [FR] COMPOSÉ DE PYRIMIDOPYRAZINE ET SON UTILISATION
  [ZH] 嘧啶并吡嗪酮化合物及其用途

  摘要：

  一种有效抑制MAT2A的新化合物，其为式III所示化合物，或者式III所示化合物的互变异构体、立体异构体、水合物、溶剂化物、药学可接受的盐或前药：其中，L1选自-O-、-S-、-N(RL1)-和单键；RL1选自氢和C1-C6烷基；R1、R2、R3、R4的定义如说明书中所述；所述化合物能够有效抑制MAT2A酶活性，具有广阔的应用前景。

  公开号：

  WO2022206730A1

文献信息

• [EN] HETERO-HALO INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS HÉTÉRO-HALOGÉNO D'HISTONE DÉSACÉTYLASE
  申请人：RODIN THERAPEUTICS INC

  公开号：WO2017007756A1

  公开（公告）日：2017-01-12

  This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula I, II or any of Compounds 100-128 or any of those in Tables 2 or 3) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.

  这项发明提供了抑制HDAC2的化合物。这些化合物（例如，符合式I、II或化合物100-128中的任何一种，或表2或3中的任何一种）可用于治疗、缓解或预防受试者的疾病，如神经系统疾病、记忆或认知功能障碍或损伤、消退学习障碍、真菌疾病或感染、炎症性疾病、血液疾病或肿瘤性疾病，或用于改善记忆或治疗、缓解或预防记忆丧失或损伤。
• Discovery of SHR5133, a Highly Potent and Novel HBV Capsid Assembly Modulator
  作者：Xin Li、Zhigao Zhang、Yang Chen、Bin Wang、Guimei Yang、Xiangbin Xu、Baihui Yechao、Dongdong Bai、Binqiang Feng、Yuchang Mao、Jun Feng、Chang Bai、Feng He、Weikang Tao

  DOI：10.1021/acsmedchemlett.2c00002

  日期：2022.3.10

  Capsid assembly modulators (CpAMs) represent a new class of antivirals targeting hepatitis B virus (HBV) core protein to disrupt the assembly process. In this work, a novel chemotype featuring a fused heterocycle amide was discovered through pharmacophore exploration. Lead optimization resulted in compound 8 with an EC50 value of 511 nM, and then methyl substitution on the piperazine was found to improve

  衣壳组装调节剂 (CpAM) 代表了一类新的抗病毒药物，靶向乙型肝炎病毒 (HBV) 核心蛋白以破坏组装过程。在这项工作中，通过药效团探索发现了一种以稠合杂环酰胺为特征的新型化学型。先导优化导致化合物8 的EC 50值为 511 nM，然后发现哌嗪上的甲基取代显着提高了体外效力。进一步的 SAR 研究确定了关键化合物 SHR5133，它显示出高体外抗病毒效力、良好的跨物种药代动力学特征和强大的体内功效。
• Bicyclic inhibitors of histone deacetylase
  申请人：Rodin Therapeutics, Inc.

  公开号：US10793567B2

  公开（公告）日：2020-10-06

  Provided are compounds of the formula and pharmaceutically acceptable salts and composition thereof, which are useful in the treatment of conditions associated with inhibition of HDAC (e.g. HDAC2).

  提供的化合物式如下 及其药学上可接受的盐和组合物，可用于治疗与抑制 HDAC（如 HDAC2）相关的疾病。
• Hetero-halo inhibitors of histone deacetylase
  申请人：Alkermes, Inc.

  公开号：US10919902B2

  公开（公告）日：2021-02-16

  This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula I, II or any of Compounds 100-128 or any of those in Tables 2 or 3) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.

  本发明提供的化合物是 HDAC2 的抑制剂。这些化合物（例如，根据式I、II或化合物100-128中的任一种或表2或表3中的任一种）相应地可用于治疗、减轻或预防受试者的病症，如神经系统疾病、记忆或认知功能障碍或损伤、消退性学习障碍、真菌疾病或感染、炎症性疾病、血液病或肿瘤性疾病，或用于改善记忆或治疗、减轻或预防记忆丧失或损伤。
• 2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity relationships
  作者：David N. Deaton、Curt D. Haffner、Brad R. Henke、Michael R. Jeune、Barry G. Shearer、Eugene L. Stewart、J. Darren Stuart、John C. Ulrich

  DOI：10.1016/j.bmc.2018.03.021

  日期：2018.5

  Starting from 4-amino-8-quinoline carboxamide lead 1a and scaffold hopping to the chemically more tractable quinazoline, a systematic exploration of the 2-substituents of the quinazoline ring, utilizing structure activity relationships and conformational constraint, resulted in the identification of 39 novel CD38 inhibitors. Eight of these analogs were 10-100-fold more potent human CD38 inhibitors, including the single digit nanomolar inhibitor 1am. Several of these molecules also exhibited improved therapeutic indices relative to hERG activity. A representative analog 1r exhibited suitable pharmacokinetic parameters for in vivo animal studies, including moderate clearance and good oral bioavailability. These inhibitor compounds will aid in the exploration of the enzymatic functions of CD38, as well as furthering the study of the therapeutic implications of NAD enhancement in metabolic disease models. (C) 2018 Elsevier Ltd. All rights reserved.