phenyl (1-methyl-1H-pyrazol-4-yl)carbamate | 1379176-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: phenyl (1-methyl-1H-pyrazol-4-yl)carbamate
• 英文别名: phenyl N-(1-methylpyrazol-4-yl)carbamate
• CAS: 1379176-31-4
• 化学式: C₁₁H₁₁N₃O₂
• mdl: MFCD20541695
• 分子量: 217.227
• InChiKey: ZPHGZPUKLGDRLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (9S)-2-(2-methylpyridin-4-yl)-7,8,9,10-tetrahydro-6H-5,9-methanopyrido[2,3-b][1,4]diazocine 、 phenyl (1-methyl-1H-pyrazol-4-yl)carbamate 在 4-二甲氨基吡啶 水 、 Brine 、 Sodium sulfate-III 、 crude compound 、 乙酸乙酯 、 正己烷 作用下， 以 四氢呋喃 、 乙酸乙酯 、 水 为溶剂， 反应 24.0h， 以to afford (9S)—N-(1-methyl-1H-pyrazol-4-yl)-2-(2-methylpyridin-4-yl)-8,9-dihydro-6H-5,9-methanopyrido[2,3-b][1,4]dia-zocine-10(7H)-carboxamide (0.17 g, 0.430 mmol, 22.89% yield) as an off-white solid, LCMS (m/z)的产率得到(9S)-N-(1-methyl-1H-pyrazol-4-yl)-2-(2-methylpyridin-4-yl)-8,9-dihydro-6H-5,9-methanopyrido[2,3-b][1,4]diazocine-10(7H)-carboxamide
  参考文献：
  名称：

  SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS

  摘要：

  本发明涉及新型取代桥联脲化合物、相应的相关类似物、制药组合物及其使用方法。本发明的Sirtuin调节化合物可用于增加细胞寿命，并治疗和/或预防各种疾病和疾病，包括但不限于与衰老或应激有关的疾病或疾病，糖尿病，肥胖症，神经退行性疾病，心血管疾病，血栓形成障碍，炎症，癌症和/或潮红，以及需要增加线粒体活性的疾病或疾病。本发明还涉及包含Sirtuin调节化合物与另一治疗剂组合的组合物。

  公开号：

  US20150152108A1
• 作为产物：
  描述：

  1-甲基-1H-吡唑-4-胺 、 氯甲酸苯酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 4.25h， 以42%的产率得到phenyl (1-methyl-1H-pyrazol-4-yl)carbamate
  参考文献：
  名称：

  [EN] SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
  [FR] ANALOGUES D'URÉE PONTÉS SUBSTITUÉS EN TANT QUE MODULATEURS DE SIRTUINE

  摘要：

  本发明涉及一种新型的取代桥式脲类似物化合物，其化学式为（I）或其药学上可接受的盐，相应的药物组合物，制备这种化合物的方法以及单独使用或与其他治疗剂联合使用的这些化合物作为Sirtuin调节剂，可用于增加细胞寿命，并用于治疗和/或预防各种疾病和紊乱，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块紊乱、炎症、癌症和/或潮红有关的疾病或紊乱，以及那些会受益于增加线粒体活性的疾病或紊乱。

  公开号：

  WO2016079709A1

文献信息

• [EN] 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'AZÉTIDINE OU DE CYCLOBUTANE 1,3-DISUBSTITUÉS UTILISÉS COMME INHIBITEURS DE LA PROSTAGLANDINE D SYNTHASE HÉMATOPOÏÉTIQUE (H-PGDS)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018069863A1

  公开（公告）日：2018-04-19

  A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式（I）的化合物，其中R、R1、R2、R3、Y、Y1、a、X和Z的定义如本文所述。本发明的化合物是造血前列腺素D合成酶（H-PGDS）的抑制剂，可用于治疗杜兴氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制H-PGDS活性和治疗相关疾病的方法。
• [EN] 4,5-DIHYDROISOXAZOLE DERIVATIVES AS NAMPT INHIBITORS<br/>[FR] DÉRIVÉS DE 4,5-DIHYDROISOXAZOLE UTILISÉS COMME INHIBITEURS DE NAMPT
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2014111871A1

  公开（公告）日：2014-07-24

  The present invention provides substituted 4,5-dihydroisoxazole derivatives of formula (I), which may be therapeutically useful, more particularly NAMPT inhibitors and in which R1 R2, Y, X, "Het" and "p" have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPT) in a mammal. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted 4,5-dihydroisoxazole derivatives of formula (I) or a pharmaceutically acceptable salts or stereoisomers or N-oxide thereof.

  本发明提供了式(I)的取代4,5-二氢异噁唑衍生物，可能在治疗上有用，更具体地是NAMPT抑制剂，其中R1、R2、Y、X、“Het”和“p”的含义如规范中所述，并且它们的药学上可接受的盐，在哺乳动物中治疗和预防由尼古酰胺磷酸核糖转移酶(NAMPT)水平升高引起的疾病或紊乱。本发明还提供了化合物的制备以及包含式(I)的取代4,5-二氢异噁唑衍生物中至少一个或其药学上可接受的盐或立体异构体或N-氧化物的制药配方。
• Substituted bridged urea analogs as sirtuin modulators
  申请人：GLAXOSMITHKLINE LLC

  公开号：US10590135B2

  公开（公告）日：2020-03-17

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥基脲化合物、相应的相关类似物、药物组合物及其使用方法。本发明的Sirtuin调节化合物可用于增加细胞的寿命，治疗和/或预防多种疾病和失调，这些疾病和失调包括但不限于例如与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、凝血障碍、炎症、癌症和/或潮红有关的疾病或失调，以及将受益于线粒体活性增加的疾病或失调。本发明还涉及由sirtuin调节化合物与另一种治疗剂组合而成的组合物。
• 1,3 di-substituted cyclobutane or azetidine derivatives as hematopoietic prostaglandin D synthase inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US11053234B2

  公开（公告）日：2021-07-06

  A compound of formula (I) wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式 (I) 的化合物 其中 R、R1、R2、R3、Y、Y1、a、X 和 Z 如本文所定义。 本发明的化合物是造血前列腺素 D 合酶（H-PGDS）的抑制剂，可用于治疗杜氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制 H-PGDS 活性和治疗相关疾病的方法。
• 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US20190241554A1

  公开（公告）日：2019-08-08

  A compound of formula (I) wherein R, R 1 , R 2 , R 3 , Y, Y 1 , a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.