phenyl (6-phenylpyridin-3-yl)carbamate | 1164113-30-7

• 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
• 英文名称: phenyl (6-phenylpyridin-3-yl)carbamate
• 英文别名: Phenyl (6-phenylpyridin-3-yl)carbamate；phenyl N-(6-phenylpyridin-3-yl)carbamate
• CAS: 1164113-30-7
• 化学式: C₁₈H₁₄N₂O₂
• 分子量: 290.321
• InChiKey: IUKYTWJFUXSECO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl (6-phenylpyridin-3-yl)carbamate 、 1-(甲基磺酰基)螺[吲哚啉-3,4’-哌啶] 在 三乙胺 作用下， 以 氯仿 为溶剂， 生成 1-(methylsulfonyl)-N-(6-phenylpyridin-3-yl)-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide
  参考文献：
  名称：

  Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists

  摘要：

  A series of spiroindoline-3,40-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats. Some of the antagonists showed good oral bioavailability and/ or good brain penetration. In particular, compound 6e was orally bioavailable and brain penetrant, and oral administration of 6e inhibited bPP-induced food intake in rats with a minimum effective dose of 10 mg/ kg. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.02.035
• 作为产物：
  描述：

  5-氨基-2-苯基吡啶 、 氯甲酸苯酯 在 吡啶 作用下， 生成 phenyl (6-phenylpyridin-3-yl)carbamate
  参考文献：
  名称：

  新型口服活性NPY Y5受体拮抗剂：螺吲哚啉类化合物的合成及其构效关系

  摘要：

  合成了设计用作NPY Y5受体拮抗剂的螺吲哚啉脲衍生物，并研究了它们的结构-活性关系。在这些衍生物中，化合物3a显示出良好的Y5结合亲和力和良好的药代动力学性质。化合物3a显着抑制了bPP Y5激动剂诱导的大鼠食物摄取，并抑制了DIO小鼠的体重增加。

  DOI：

  10.1016/j.bmc.2009.05.064

文献信息

• Novel orally active NPY Y5 receptor antagonists: Synthesis and structure–activity relationship of spiroindoline class compounds
  作者：Toshihiro Sakamoto、Minoru Moriya、Hiroyasu Tsuge、Toshiyuki Takahashi、Yuji Haga、Katsumasa Nonoshita、Osamu Okamoto、Hirobumi Takahashi、Aya Sakuraba、Tomoko Hirohashi、Takunobu Shibata、Tetsuya Kanno、Junko Ito、Hisashi Iwaasa、Akira Gomori、Akane Ishihara、Takahiro Fukuroda、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmc.2009.05.064

  日期：2009.7

  Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure–activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic properties. Compound 3a significantly inhibited bPP Y5 agonist-induced food intake in rats, and suppressed body weight gain in DIO mice.

  合成了设计用作NPY Y5受体拮抗剂的螺吲哚啉脲衍生物，并研究了它们的结构-活性关系。在这些衍生物中，化合物3a显示出良好的Y5结合亲和力和良好的药代动力学性质。化合物3a显着抑制了bPP Y5激动剂诱导的大鼠食物摄取，并抑制了DIO小鼠的体重增加。
• [EN] TREATMENT OF MYC-DRIVEN CANCERS WITH GSPT1 DEGRADERS<br/>[FR] TRAITEMENT DE CANCERS ENTRAÎNÉS PAR MYC AVEC DES AGENTS DE DÉGRADATION GSPT1
  申请人：MONTE ROSA THERAPEUTICS AG

  公开号：WO2022152822A1

  公开（公告）日：2022-07-21

  The present disclosure relates to new methods to predict the responsiveness of cancer patients to GSPT1 negative modulators and thus determine the of efficacy GSPT1 negative modulators to treat cancer patients by determining the level of one or more biomarkers in samples of the patients. The present disclosure also relates to applications of these methods, which includes stratifying cancer malignancies, in particular identifying myc-driven cancers, and thereby devising optimized and personalized treatments for these cancer patients, as well as optimizing the selection of patient populations for respective clinical trials.

  本公开涉及新的方法来预测癌症患者对GSPT1负调节剂的反应性，从而通过确定患者样本中一个或多个生物标志物的水平来确定GSPT1负调节剂治疗癌症患者的有效性。本公开还涉及这些方法的应用，包括分层癌症恶性程度，特别是识别驱动肿瘤的myc，从而为这些癌症患者设计优化和个性化的治疗方案，以及优化选择患者人群进行相应的临床试验。
• [EN] ISOINDOLINONE COMPOUNDS<br/>[FR] COMPOSÉS D'ISOINDOLINONE
  申请人：MONTE ROSA THERAPEUTICS AG

  公开号：WO2022152821A1

  公开（公告）日：2022-07-21

  Disclosed herein are compound or pharmaceutically acceptable salts or stereoisomers thereof of formula (I). These compounds find use as modulators of cereblon, in particular in the treatment of abnormal cell growth in mammals, especially humans.

  本文揭示了公式(I)的化合物或药学上可接受的盐或其立体异构体。这些化合物可用作 cereblon 调节剂，特别是用于治疗哺乳动物，尤其是人类的异常细胞生长。
• [EN] PHARMACEUTICAL COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF A DISEASE OR DISORDER CAUSED BY OR ASSOCIATED WITH ONE OR MORE PREMATURE TERMINATION CODONS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DESTINÉES À ÊTRE UTILISÉES POUR PRÉVENIR OU TRAITER UNE MALADIE OU UN TROUBLE PROVOQUÉ PAR OU ASSOCIÉ À UN OU PLUSIEURS CODONS DE TERMINAISON PRÉMATURÉS
  申请人：MONTE ROSA THERAPEUTICS AG

  公开号：WO2022200857A1

  公开（公告）日：2022-09-29

  The present disclosure relates to a. compound of formula I or a. pharmaceutically acceptable salt thereof Formula I wherein A is Formula II X1is linear or branched C1-6alkyl, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X1is unsubstituted or substituted with one or more of halogen, linear or branched C1-6alkyl, linear or branched C1-6heteroalkyl, CF3, CHF2, CMeF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6alkylamino, -CN, -N(H)C(O)-C1-6alkyl, - OC(O)-C1-6alkyl, -OC(O)-C1-4alkylamino, -C(O)O-C1-6alkyl, -COOH, -CHO, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-6alkoxy or Cue alkylhydroxy; or X1together with X4forms a 4-8 membered heterocycloalkyl, which is unsubstituted or substituted with one or more of halogen, linear or branched -C1-6alkyl, CF3, CHF2, CMeF2, -O-(CH2)2-OMe, OCF3, OCHF2, C1-6alkylamino, -CN, -N(H)C(O)-C1-6alkyl, -OC(O)-C1-6alkyl, -C(O)O-C1-6alkyl, -COOH, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-4alkylhydroxy, or C1-4alkoxy; X2is hydrogen, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X2is unsubstituted or substituted with one or more of linear or branched Cue alkyl, -C1-4alkoxy, NH2, NMe2, halogen, CF3, CHF2, CMeF2, -O-(CH2)2-OMe, OCF3, OCHF2, CM alkylhydroxy, X3is -NH-, -O-; X4is -NH-, - CH2-; L1is a covalent bond, C1-6alkyl, which is unsubstituted or substituted with one or more of C1-4alkyl, halogen; L2is a covalent bond, Cue alkyl, which is unsubstituted or substituted with one or more of CM alkyl, halogen; L3is a covalent bond, -O-, - C1-4alkoxy or C1-6alkyl, which is unsubstituted or substituted with one or more of C1-4alkyd, halogen, for use in the prevention and treatment of a disease or disorder caused by or associated with one or more premature termination codons in a monotherapy or in a combined therapy with an aminoglycoside or a. pharmaceutically acceptable salt thereof.

  本公开涉及式I的化合物或其药学上可接受的盐，其中A为式II，X1为线性或支链C1-6烷基，C3-6环烷基，C6-10芳基，5-10成员杂芳基，4-8成员杂环烷基，其中X1未取代或取代有卤素，线性或支链C1-6烷基，线性或支链C1-6杂烷基，CF3，CHF2，CMeF2，-O-CHF2，-O-(CH2)2-OMe，OCF3，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-OC(O)-C1-4烷基氨基，-C(O)O-C1-6烷基，-COOH，-CHO，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-6烷氧基或Cue烷基羟基；或X1与X4共同形成未取代或取代有卤素，线性或支链C1-6烷基，CF3，CHF2，CMeF2，-O-(CH2)2-OMe，OCF3，OCHF2，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-C(O)O-C1-6烷基，-COOH，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-4烷基羟基或C1-4烷氧基的4-8成员杂环烷基；X2为氢，C3-6环烷基，C6-10芳基，5-10成员杂芳基，4-8成员杂环烷基，其中X2未取代或取代有线性或支链Cue烷基，-C1-4烷氧基，NH2，NMe2，卤素，CF3，CHF2，CMeF2，-O-(CH2)2-OMe，OCF3，OCHF2，CM烷基羟基，X3为-NH-，-O-；X4为-NH-，-CH2-；L1为共价键，C1-6烷基，未取代或取代有C1-4烷基，卤素；L2为共价键，Cue烷基，未取代或取代有CM烷基，卤素；L3为共价键，-O-，-C1-4烷氧基或C1-6烷基，未取代或取代有C1-4烷基，卤素，用于单一疗法或与氨基糖苷类药物或其药学上可接受的盐联合疗法预防和治疗由一个或多个过早终止密码子引起或相关的疾病或障碍。
• [EN] ISOINDOLINONE COMPOUNDS<br/>[FR] COMPOSÉS D'ISO-INDOLINONE
  申请人：MONTE ROSA THERAPEUTICS AG

  公开号：WO2022219407A1

  公开（公告）日：2022-10-20

  Disclosed herein are compound or pharmaceutically acceptable salts or stereoisomers thereof of Formula (I), wherein X1is selected from the group consisting of linear or branched C1-6alkyl, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, and 4-8 membered heterocycloalkyl, wherein X1is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, linear or branched C1-6alkyl, linear or branched C1-6heteroalkyl, CF3, CHF2, CMeF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6alkylamino, -CN, NH2, C1-4alkoxy and C1-4alkylhydroxy; X2is selected from the group consisting of H, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, and 4-8 membered heterocycloalkyl, wherein X2is unsubstituted or substituted with one or more substituents independently selected from the group consisting of linear or branched C1-6alkyl, -C1-4alkoxy, NH2, NMe2, halogen, CF3, CHF2, CMeF2, -O-(CH2)2-OMe, OCF3, OCHF2, and C1-4alkylhydroxy; Y is selected from the group consisting of linear or branched C1-6alkyl, -C1-4alkoxy, -CN, halogen, CF3,CHF2, CMeF2, OCF3, and OCHF2; L1is linear or branched C1-6alkyl; L2is selected from a covalent bond, and linear or branched C1-6alkyl; and L3is selected from the group consisting of a covalent bond, linear or branched C1-6alkyl, -O-, and -C1-4alkoxy. Disclosed herein is also their use as modulators of cereblon, methods of preparation of these compounds, compositions comprising these compounds, and methods of using them in the treatment of abnormal cell growth in mammals, especially humans.

  本文披露了式（I）的化合物或药学上可接受的盐或其立体异构体，其中X1选自线性或支链C1-6烷基，C3-6环烷基，C6-10芳基，5-10成员杂芳基和4-8成员杂环烷基的群，其中X1未取代或取代有一个或多个取代基，独立地选自卤素，线性或支链C1-6烷基，线性或支链C1-6杂烷基，CF3，CHF2，CMeF2，-O-CHF2，-O-（CH2）2-OMe，OCF3，C1-6烷基氨基，-CN，NH2，C1-4烷氧基和C1-4烷基羟基；X2选自H，C3-6环烷基，C6-10芳基，5-10成员杂芳基和4-8成员杂环烷基的群，其中X2未取代或取代有一个或多个取代基，独立地选自线性或支链C1-6烷基，-C1-4烷氧基，NH2，NMe2，卤素，CF3，CHF2，CMeF2，-O-（CH2）2-OMe，OCF3，OCHF2和C1-4烷基羟基；Y选自线性或支链C1-6烷基，-C1-4烷氧基，-CN，卤素，CF3，CHF2，CMeF2，OCF3和OCHF2的群；L1为线性或支链C1-6烷基；L2选自共价键和线性或支链C1-6烷基；L3选自共价键，线性或支链C1-6烷基，-O-和-C1-4烷氧基的群。本文还披露了它们作为小脑蛋白调节剂的用途，这些化合物的制备方法，包含这些化合物的组合物以及在哺乳动物，特别是人类的异常细胞生长治疗中使用它们的方法。