N-benzyl-1-propyl-4-piperidinamine | 683271-61-6

• 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: N-benzyl-1-propyl-4-piperidinamine
• 英文别名: N-benzyl-1-propylpiperidin-4-amine
• CAS: 683271-61-6
• 化学式: C₁₅H₂₄N₂
• mdl: MFCD11140730
• 分子量: 232.369
• InChiKey: QSJXFJNMZMPGPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzyl-1-propyl-4-piperidinamine 、 3-(三氟甲基)异氰酸苯酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 1-benzyl-1-(1-propylpiperidin-4-yl)-3-(3-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation

  摘要：

  We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit. The optimized compounds inhibit the DCN1- UBE2M protein-protein interaction in our TR-FRET binding assay and inhibit cullin neddylation in our pulse-chase NEDD8 transfer assay. The optimized compounds bind to DCN1 and selectively reduce steady-state levels of neddylated CUL1 and CUL3 in a squamous cell carcinoma cell line. Ultimately, we anticipate that these studies will identify early lead compounds for clinical development for the treatment of lung squamous cell carcinomas and other cancers.

  DOI：

  10.1021/acs.jmedchem.7b01277
• 作为产物：
  描述：

  4-哌啶酮 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 N-benzyl-1-propyl-4-piperidinamine
  参考文献：
  名称：

  Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation

  摘要：

  We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit. The optimized compounds inhibit the DCN1- UBE2M protein-protein interaction in our TR-FRET binding assay and inhibit cullin neddylation in our pulse-chase NEDD8 transfer assay. The optimized compounds bind to DCN1 and selectively reduce steady-state levels of neddylated CUL1 and CUL3 in a squamous cell carcinoma cell line. Ultimately, we anticipate that these studies will identify early lead compounds for clinical development for the treatment of lung squamous cell carcinomas and other cancers.

  DOI：

  10.1021/acs.jmedchem.7b01277

文献信息

• Benzyl substituted (piperidin-4-yl)aminobenzamido derivatives
  申请人：——

  公开号：US20040082612A1

  公开（公告）日：2004-04-29

  The present invention is directed to N-benzyl substituted (piperidin-4-yl)aminobenzamido derivatives which are delta-opioid receptor modulators.

  本发明涉及N-苄基取代的（哌啶-4-基）氨基苯甲酰胺衍生物，其为δ-阿片受体调节剂。
• Methods and compositions of inhibiting DCN1-UBC12 interaction
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：US11116757B2

  公开（公告）日：2021-09-14

  In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及取代的1-苯基-3-(哌啶-4-基)脲类似物、其衍生物和相关化合物，它们可用作DCN1-UBC12相互作用的抑制剂DCN1介导的cullin-RING连接酶活性的抑制剂、制造方法、包含它们的药物组合物、使用所公开的化合物和组合物治疗疾病的方法、治疗与DCN1-UBC12相互作用功能障碍相关的疾病的方法、治疗与DCN1介导的cullin-RING连接酶活性障碍相关的疾病的方法、包含所公开化合物和组合物的男性避孕方法，以及包含所公开化合物和组合物的试剂盒。本摘要旨在作为在特定技术领域进行搜索的扫描工具，并非对本发明的限制。
• METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：US20180256558A1

  公开（公告）日：2018-09-13

  In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• US7576105B2
  申请人：——

  公开号：US7576105B2

  公开（公告）日：2009-08-18
• [EN] BENZYL SUBSTITUTED (PIPERIDIN-4-YL) AMINOBENZAMIDO DERIVATIVES AS DELTA-OPIOD RECEPTOR MODULATORS<br/>[FR] DERIVES (PIPERIDINE-4-YL)-AMINOBENZAMIDO A SUBSTITUTION BENZYL SERVANT DE MODULATEURS DE RECEPTEURS DELTA-OPIOIDES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004035541A1

  公开（公告）日：2004-04-29

  The present invention is directed to N-benzyl substituted (piperidin-4-yl)aminobenzamido derivatives which are delta-opioid receptor modulators.