Phenyl [4-(dimethylamino)phenyl]carbamate | 20950-93-0

• 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 [4-(dimethylamino)phenyl]carbamate
• 英文别名: phenyl N-[4-(dimethylamino)phenyl]carbamate
• CAS: 20950-93-0
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: ONMIXKXTPKQWAZ-UHFFFAOYSA-N

物化性质

• 沸点：
  379.6±34.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Phenyl [4-(dimethylamino)phenyl]carbamate 、 4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)aniline 在 1-甲基吡咯烷 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 N-((4-dimethylamino)phenyl)-N'-(4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)urea
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468
• 作为产物：
  描述：

  N,N-二甲基对硝基苯胺 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 Phenyl [4-(dimethylamino)phenyl]carbamate
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468

文献信息

• Semicarbazide derivatives, processes for preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0144853A2

  公开（公告）日：1985-06-19

  New semicarbazide derivatives of the formula: wherein R' is hydrogen, R2 is hydrogen, lower alkyl, ar(lower)alkyl, lower alkenyl or aryl, R3 is lower alkyl, ar(lower)alkyl, lower alkenyl or aryl, or R2 and R3 are taken together to form (C2-C6)-alkylidene group optionally substituted with aryl or taken together with the adjacent nitrogen atom to form a saturated or unsaturated, 5- or 6-membered heterocyclic group optionally substituted with aryl; or R' and R2 are taken together with the adjacent nitrogen atoms to form a saturated or unsaturated, 5- or 6-membered heterocyclic group or 1,2-diazaspiroalkane-1,2-diyl group, R3 is hydrogen, lower alkyl, ar(lower)alkyl, lower alkeny or aryl; R4 is aryl which may have substituent(s) selected from lower alkyl, halogen, lower alkoxy, lower alkylamino, halo(lower)alkyl, hydroxy, lower alkanoyl, esterified carboxy and carboxy, R5 is hydrogen or lower alkyl, and X is 0 or S, provided that the lower alkyl group for R3 is (C3-C6) alkyl, when R2 is hydrogen or (C1-C2) alkyl and R4 is aryl optionally having substituent(s) selected from groups consisting of halogen, lower alkyl, lower alkoxy and halo(lower)alkyl, and pharmaceutically acceptable salts thereof, and processes for preparation thereof and pharmaceutical composition comprising the same. These derivatives and salts thereof are useful as antiinflammatory and analgesic agents.

  式中的新半咔嗪衍生物： 式中 R'是氢 R2 是氢、低级烷基、低级烯基或芳基、 R3 是低级烷基、芳（低）烷基、低级烯基或芳基，或 R2 和 R3 共同形成可选择被芳基取代的 (C2-C6)- 亚烷基，或与邻近的氮原子共同形成可选择被芳基取代的饱和或不饱和 5 或 6 元杂环基团；或 R' 和 R2 与相邻的氮原子结合形成饱和或不饱和的 5 或 6 元杂环基团或 1,2-二氮杂螺烷-1,2-二基、 R3 是氢、低级烷基、芳（低）烷基、低级烯基或芳基； R4 是芳基，可具有选自低级烷基、卤素、低级烷氧基、低级烷基氨基、卤代（低级）烷基、羟基、低级烷酰基、酯化羧基和羧基的取代基、 R5 是氢或低级烷基，以及 X是0或S，条件是R3的低级烷基是(C3-C6)烷基，当R2是氢或(C1-C2)烷基和R4是芳基时，可选择具有选自卤素、低级烷基、低级烷氧基和卤代（低级）烷基组成的基团的取代基，及其药学上可接受的盐，以及其制备工艺和由其组成的药物组合物。 这些衍生物及其盐类可用作抗炎和镇痛剂。
• CYCLOHEXANEDIUREA DERIVATIVE AND PROCESS FOR PRODUCING THE SAME
  申请人：NISSIN FOOD PRODUCTS CO., LTD.

  公开号：EP0718281A1

  公开（公告）日：1996-06-26

  The present invention provides a cyclohexanediurea derivative, inclusive of its salt, represented by the following formula (I): wherein R¹ and R² are the same or different and they each represent a straight-chain or branched alkyl group having at least 3 carbons, a cycloalkyl group, a cycloalkyl group having a bridge head, a furyl group, a furyl lower alkyl group or an aralkyl group, A₁ and A₂ are the same or different and they each represent a phenyl, pyridyl, quinolyl, isoquinolyl or indolyl group which may have substituents; a process for production thereof; an intermediate thereof; pharmaceutical use, a method for treatment and use thereof.

  本发明提供了由下式（I）表示的环己烷二脲衍生物，包括其盐： 其中 R¹ 和 R² 相同或不同，它们各自代表至少具有 3 个碳原子的直链或支链烷基、环烷基、具有桥头的环烷基、呋喃基、呋喃低级烷基或芳烷基，A₁ 和 A₂ 相同或不同，它们各自代表可能具有取代基的苯基、吡啶基、喹啉基、异喹啉基或吲哚基；其生产工艺；其中间体；其医药用途、治疗方法和使用方法。
• Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy
  作者：Qi Lv、Hongqiong Yang、Dan Wang、Haikun Zhou、Juan Wang、Yishu Zhang、Dapeng Wu、Ying Xie、Yingshan Lv、Lihong Hu、Junwei Wang

  DOI：10.1021/acs.jmedchem.4c00508

  日期：2024.4.25

  CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor C19 with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. C19 could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME

  阻断 CSF-1/CSF-1R 通路已成为通过重新编程肿瘤相关巨噬细胞 (TAM) 来重塑肿瘤免疫微环境 (TME) 的有前途的策略。在这项工作中，成功发现了一种新型 CSF-1R 抑制剂C19 ，其具有显着改善的药代动力学特征和体内抗结直肠癌 (CRC) 功效。 C19可以有效地将 M2 样 TAM 重编程为 M1 表型，并通过诱导 CD8 + T 细胞招募到肿瘤中并减少免疫抑制性 Tregs/MDSC 的浸润来重塑 TME。更深入的机制研究表明， C19通过增强趋化因子 CXCL9 的分泌来促进 CD8 + T 细胞的浸润，从而显着增强 PD-1 阻断的抗 CRC 效率。更重要的是， C19联合PD-1 mAb可以诱导持久的抗肿瘤免疫记忆，有效克服CRC的复发。综上所述，我们的研究结果表明， C19是一种有前途的治疗选择，可以提高 CRC 对抗 PD-1 疗法的敏感性。
• US4725608A
  申请人：——

  公开号：US4725608A

  公开（公告）日：1988-02-16
• US5733931A
  申请人：——

  公开号：US5733931A

  公开（公告）日：1998-03-31