N-[4-(氨基甲基)苯基]-甲烷磺酰胺 | 129872-50-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[4-(氨基甲基)苯基]-甲烷磺酰胺
• 中文别名: 甲烷磺酰胺,N-[4-(氨基甲基)苯基]-
• 英文名称: N-<4-(aminomethyl)phenyl>methanesulfonamide
• 英文别名: N-(4-(aminomethyl)benzyl)methanesulfonamide；N-(4-(aminomethyl)phenyl)methanesulfonamide；N-[4-(aminomethyl)phenyl]methanesulfonamide；N-(4-aminomethylphenyl)methanesulfonamide；4-(methylsulfonylamino)benzylamine；N-(4-aminomethylphenyl)-methanesulfonamide
• CAS: 129872-50-0
• 化学式: C₈H₁₂N₂O₂S
• mdl: MFCD06212900
• 分子量: 200.261
• InChiKey: IZJVPNBRAKIMBK-UHFFFAOYSA-N

物化性质

• 熔点：
  255-257 °C
• 沸点：
  353.9±44.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[4-(氨基甲基)苯基]-甲烷磺酰胺 在 一水合肼 、 三乙胺 、 2,3-二脱氧胞啶 作用下， 以 二氯甲烷 、 二甲基亚砜 、 异丙醇 、 甲苯 为溶剂， 生成 N-[4-[[[3-[5-(1,3-benzodioxol-5-ylamino)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]amino]methyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines

  摘要：

  Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 mu M. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.11.094
• 作为产物：
  描述：

  N-BOC-4-硝基苄胺 在 palladium on activated charcoal 吡啶 、 氢气 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-[4-(氨基甲基)苯基]-甲烷磺酰胺
  参考文献：
  名称：

  Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects

  摘要：

  A novel non-vanilloid VR1 antagonist consisting of a new vanilloid equivalent exhibits excellent analgesic effects as well as highly potent antagonistic activities in both capsaicin single channel and calcium uptake assays. In addition, the structural requirement for the vanilloid equivalent of the potent VR1 antagonist has also been elucidated. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.024

文献信息

• Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists
  作者：Nannan Sun、Yafei Huang、Mingcheng Yu、Yunpeng Zhao、Ji-An Chen、Chenyu Zhu、Meiqi Song、Huimin Guo、Qiong Xie、Yonghui Wang

  DOI：10.1016/j.ejmech.2020.112536

  日期：2020.9

  GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered

  GSK805（1）是一种强效RORγt反向激动剂，但缺点1是它的低溶解度，从而导致在高剂量有限的吸收。我们已经探索了1的酰胺连接基，联芳基和芳基磺酰基部分的详细结构-活性关系，试图在保持RORγt活性的同时提高溶解度。结果，发现了一系列新颖的含羧基联芳基脲衍生物，作为具有改进的类药物性质的有效RORγt反向激动剂。化合物3i显示了强大的RORγt抑制活性和亚型选择性，在RORγFRET分析中的IC 50为63.8 nM，在基于细胞的RORγ-GAL4启动子报告子分析中为85 nM。合理的3i抑制活性在小鼠Th17细胞分化试验中也获得了抑制（在0.3μM时抑制76％）。此外，与1相比，3i在pH 7.4时具有大大改善的水溶解度，表现出体面的小鼠PK曲线，并在咪喹莫特诱导的牛皮癣小鼠模型中表现出一定的体内功效。
• TRPV1 ANTAGONISTS
  申请人：AbbVie Inc.

  公开号：US20130345255A1

  公开（公告）日：2013-12-26

  Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, prodrugs, or combinations thereof, wherein X 1 , L, R x , R y , R z , R 1 , R 2 , A, m, n, p, q, and r are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文披露了具有以下结构的化合物（I）或药用盐、前药或其组合物，其中X1、L、Rx、Ry、Rz、R1、R2、A、m、n、p、q和r在规范中有定义。还披露了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。
• [EN] ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'ADÉNINE EN TANT QU'INHIBITEURS DE PROTÉINE KINASES
  申请人：BCI PHARMA

  公开号：WO2017191297A1

  公开（公告）日：2017-11-09

  The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.

  本发明涉及一种适用于作为激酶抑制剂的化合物，其符合一般式(I) [化合物(C)，以下简称]，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体，式(I)中A、R1、R2、R3、R3'、R4、R4'、X、Y、Z、T的定义如权利要求所述。本发明还涉及一种体外抑制蛋白激酶活性的方法，包括将蛋白激酶与式(I)的化合物，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体接触。本发明还涉及式(I)的化合物本身，以及其作为药物的用途，以及用于治疗由蛋白激酶介导的疾病的方法，所述疾病包括癌症、炎症性疾病、心血管疾病、病毒感染性疾病、循环系统疾病、纤维增殖性疾病和疼痛敏化性疾病。
• High Affinity Antagonists of the Vanilloid Receptor
  作者：Yun Wang、Tamas Szabo、Jacqueline D. Welter、Attila Toth、Richard Tran、Jiyoun Lee、Sang Uk Kang、Young-Ger Suh、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1124/mol.62.4.947

  日期：2002.10.1

  The vanilloid receptor VR1 has attracted great interest as a sensory transducer for capsaicin, protons, and heat, and as a therapeutic target. Here we characterize two novel VR1 antagonists, KJM429 [ N -(4- tert -butylbenzyl)- N ′-[4-(methylsulfonylamino)benzyl]thiourea] and JYL1421 [ N -(4- tert -butylbenzyl)- N ′-[3-fluoro-4-(methylsulfonylamino)benzyl]thiourea], with enhanced activity compared with capsazepine on rat VR1 expressed in Chinese hamster ovary (CHO) cells. JYL1421, the more potent of the two novel antagonists, inhibited [3H]resiniferatoxin binding to rVR1 with an affinity of 53.5 ± 6.5 nM and antagonized capsaicin-induced calcium uptake with an EC50 of 9.2 ± 1.6 nM, reflecting 25- and 60-fold greater potencies than capsazepine. Both JYL1421 and KJM429 antagonized RTX as well as capsaicin and their mechanism was competitive. The responses to JYL1421 and KJM429 differed for calcium uptake by rVR1 induced by heat or pH. JYL1421 antagonized the response to both pH 6.0 and 5.5, whereas KJM429 antagonized at pH 6.0 but was an agonist at lower pH (<5.5). For heat, JYL1421 fully antagonized and KJM429 partially antagonized. Capsazepine showed only weak antagonism for both pH and heat. Responses of rVR1 to different activators could thus be differentially affected by different ligands. In cultured dorsal root ganglion neurons, JYL1421 and KJM429 likewise behaved as antagonists for capsaicin, confirming that the antagonism is not limited to heterologous expression systems. Finally, JYL1421 and KJM429 had little or no effect on ATP-induced calcium uptake in CHO cells lacking rVR1, unlike capsazepine. We conclude that JYL1421 is a competitive antagonist of rVR1, blocking response to all three of the agonists (capsaicin, heat, and protons) with enhanced potency relative to capsazepine.

  香草素受体VR1因其作为辣椒素、质子和热的传感转换器以及作为治疗靶点而引起了极大的兴趣。在这里，我们描述了两种新的VR1拮抗剂，KJM429[N-(4-叔丁基苄基)-N′-[4-(甲磺酰氨基)苄基]硫脲]和JYL1421[N-(4-叔丁基苄基)-N′-[3-氟-4-(甲磺酰氨基)苄基]硫脲]，它们在大鼠VR1在中国仓鼠卵巢(CHO)细胞中表达时，活性比capsazepine更强。在这两种新型拮抗剂中，JYL1421的活性更强，它抑制[3H]树脂毒素与rVR1的结合，亲和力为53.5±6.5 nM，并拮抗辣椒素诱导的钙吸收，EC50为9.2±1.6 nM，反映出比capsazepine强25倍和60倍的效力。JYL1421和KJM429均能拮抗RTX和辣椒素，其机制为竞争性。JYL1421和KJM429在钙吸收上的反应不同，前者对热或pH诱导的rVR1反应产生拮抗或激动作用。JYL1421拮抗pH 6.0和5.5的反应，而KJM429在pH 6.0时拮抗，但在更低的pH(<5.5)时为激动剂。对于热刺激，JYL1421完全拮抗，而KJM429部分拮抗。Capsazepine对pH和热的拮抗作用很弱。因此，rVR1对不同激动剂的反应可以被不同的配体不同程度地影响。在培养的背根神经节神经元中，JYL1421和KJM429同样表现为辣椒素的拮抗剂，证实了这种拮抗作用不仅限于异源表达系统。最后，与capsazepine不同，JYL1421和KJM429对缺乏rVR1的CHO细胞中的ATP诱导的钙吸收几乎没有影响。我们得出结论，JYL1421是rVR1的竞争性拮抗剂，相对于capsazepine，它阻止了对所有三种激动剂(辣椒素、热和质子)的反应，并增强了效力。
• [EN] PYRAZOLO[3,4-b]PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] COMPOSES DE PYRAZOLO[3,4-b]PYRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2005090353A1

  公开（公告）日：2005-09-29

  The invention relates to a compound of formula (I) or a salt thereof: formula (I) wherein: R1 is Et, n-Pr, i-Pr, C2fluoroalkyl, or -CH2CH2OH; R2 is H, Me, Et, n-Pr, i-Pr, C1-2fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-; and NHR3 has the sub-formula (nhr3): formula (nhr3) wherein R3a is methyl or ethyl; R3b is H, methyl or ethyl; R3c is H, methyl or ethyl, R3d is H, methyl or ethyl, and R3e is H or methyl, provided that: (a) R3b is methyl or ethyl; and/or (b) R3c and R3d are independently methyl or ethyl; and provided that: (c) when R3c is ethyl and/or when R3d is ethyl and/or when R3e is methyl, then: R3a is methyl and/or R3b is a hydrogen atom (H) or methyl. NHR3 can for example be [(1S)-1,2-dimethylpropyl]amino or t-butylamino. The invention also relates to the use of these pyrazolo[3,4 b]pyridine compounds in therapy, as inhibitors of phosphodiesterase type IV (PDE4), and relates to their use in the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis or allergic rhinitis.

  该发明涉及公式（I）的化合物或其盐：公式（I）其中：R1为Et、n-Pr、i-Pr、C2氟烷基或-CH2CH2OH；R2为H、Me、Et、n-Pr、i-Pr、C1-2氟烷基、环丙基或（环丙基）甲基-；NHR3具有亚公式（nhr3）：公式（nhr3）其中R3a为甲基或乙基；R3b为H、甲基或乙基；R3c为H、甲基或乙基，R3d为H、甲基或乙基，R3e为H或甲基，条件是：（a）R3b为甲基或乙基；和/或（b）R3c和R3d独立为甲基或乙基；并且条件是：（c）当R3c为乙基和/或当R3d为乙基和/或当R3e为甲基时，则：R3a为甲基和/或R3b为氢原子（H）或甲基。NHR3可以例如是[(1S)-1,2-二甲基丙基]氨基或叔丁基氨基。该发明还涉及将这些吡唑并[3,4 b]吡啶化合物用于治疗，作为磷酸二酯酶IV（PDE4）的抑制剂，并涉及它们在治疗和/或预防炎症和/或过敏疾病如慢性阻塞性肺病（COPD）、哮喘、类风湿性关节炎或过敏性鼻炎中的用途。