1-(1-benzylpiperidin-4-yl)-3-phenylurea | 41220-40-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(1-benzylpiperidin-4-yl)-3-phenylurea
• 英文别名: N-(1-Benzyl-4-piperidyl)-N'-phenylurea；3-(1-Benzylpiperidin-4-yl)-1-phenylurea
• CAS: 41220-40-0
• 化学式: C₁₉H₂₃N₃O
• mdl: MFCD00249080
• 分子量: 309.411
• InChiKey: FBRUCPZAISLOOV-UHFFFAOYSA-N

物化性质

• 熔点：
  170 °C(Solv: ethanol (64-17-5); ethyl acetate (141-78-6))
• 沸点：
  438.5±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.315
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-苄基-4-(Boc-氨基)哌啶 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 1-(1-benzylpiperidin-4-yl)-3-phenylurea
  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

• [EN] METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS D'INHIBITION DE L'INTERACTION DCN1-UBC12
  申请人：ST JUDE CHILDREN'S RES HOSPITAL

  公开号：WO2017049295A1

  公开（公告）日：2017-03-23

  In one aspect, the invention relates to substituted l-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，本发明涉及替代的l-苯基-3-(哌啶-4-基)脲类似物，其衍生物和相关化合物，这些化合物可用作DCN1-UBC12相互作用抑制剂和DCN1介导的卡林-环形酶活性抑制剂，制备方法，包含这些化合物的药物组合物，使用所披露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介导的卡林-环形酶活性功能障碍相关的疾病的方法，包含所披露的化合物和组合物的男性避孕方法，以及包含所披露的化合物和组合物的试剂盒。本摘要旨在作为在特定领域进行搜索的扫描工具，并不打算限制本发明。
• Use of substituted chromans, some of which are known, as medicaments,
  申请人：Bayer Aktiengesellschaft

  公开号：US05492918A1

  公开（公告）日：1996-02-20

  The present invention relates to the use of substituted chromans of the general formula (I) ##STR1## in which the substituents have the meaning indicated in the description, for the production of medicaments, in particular as HIV protease-inhibiting agents, new active compounds and processes for their preparation.

  本发明涉及使用一般式（I）##STR1##中的取代色苷，其中取代基具有描述中指示的含义，用于生产药物，特别是作为HIV蛋白酶抑制剂的药物，以及新的活性化合物和其制备方法。
• 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。
• 1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1,3-dihydroimidazol-2-one:  A Selective High-Affinity Antagonist for the Human Dopamine D₄ Receptor with Excellent Selectivity over Ion Channels
  作者：Robert W. Carling、Kevin W. Moore、Christopher R. Moyes、Elizabeth A. Jones、Katrine Bonner、Frances Emms、Rosemary Marwood、Shil Patel、Smita Patel、Alan E. Fletcher、Margaret Beer、Bindi Sohal、Andrew Pike、Paul D. Leeson

  DOI：10.1021/jm991029k

  日期：1999.7.1

  After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1,3-dihydroimidazol-2-yl)piperidine . Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot'' procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1,3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or B-position of the 1,3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater Selectivity( > 1000-foId) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has > 1000-fold selectivity over-all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D-4 receptor.
• METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION
  申请人：St. Jude Children's Research Hospital

  公开号：EP3349743A1

  公开（公告）日：2018-07-25