3-氟-4-(甲基磺酰基氨基)苄胺 | 565448-36-4

• 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: 3-氟-4-(甲基磺酰基氨基)苄胺
• 英文名称: 3-fluoro-4-(methylsulfonylamino)benzylamine
• 英文别名: N-(4-(aminomethyl)-2-fluorophenyl)methanesulfonamide；N-[3-fluoro-4-(methylsulfonylamino)benzyl]hydroxylamine；N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide
• CAS: 565448-36-4
• 化学式: C₈H₁₁FN₂O₂S
• 分子量: 218.252
• InChiKey: NJJHDEAXOFVGBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 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：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-(tert-butyl)phenyl)-2-isothiocyanatoethyl pivalate 、 3-氟-4-(甲基磺酰基氨基)苄胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 [2-(4-Tert-butylphenyl)-2-[[3-fluoro-4-(methanesulfonamido)phenyl]methylcarbamothioylamino]ethyl] 2,2-dimethylpropanoate
  参考文献：
  名称：

  Structure–activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism

  摘要：

  The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino) benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.034
• 作为产物：
  描述：

  2-氟-4-碘苯胺 在 吡啶 、 甲醇 、 四(三苯基膦)钯 、 氨 、 镍 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、206.85 kPa 条件下， 反应 9.0h， 生成 3-氟-4-(甲基磺酰基氨基)苄胺
  参考文献：
  名称：

  TRPV1 ANTAGONISTS

  摘要：

  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。

  公开号：

  US20130345255A1

文献信息

• [EN] NOVEL N-HYDROXY THIOUREA, UREA AND AMIDE COMPOUNDS AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] NOUVEAUX COMPOSES DE N-HYDROXYTHIOUREE, D'UREE ET AMIDES ET LES COMPOSITIONS PHARMACEUTIQUES LES RENFERMANT
  申请人：DIGITAL BIOTECH CO LTD

  公开号：WO2004035533A1

  公开（公告）日：2004-04-29

  The present invention relates to novel n-hydroxythiourea, urea and amide compounds as a potent vanilloid receptor antagonist and the pharmaceutical compositions comprising the same. The inventive compound can be useful for analgesics to prevent, alleviate or treat pain diseases or inflammatory disease comprising pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease, inflammatory disease and urgent urinary incontinence.

  本发明涉及新型n-羟基硫脲、尿素和酰胺化合物，作为有效的辣椒素受体拮抗剂，以及包含这些化合物的药物组合物。这种创新化合物可用于镇痛药，用于预防、缓解或治疗疼痛疾病或包括疼痛的炎症性疾病，如急性疼痛、慢性疼痛、神经痛、术后疼痛、偏头痛、关节痛、神经病、神经损伤、糖尿病性神经病、神经退行性疾病、神经性皮肤疾病、中风、尿道膀胱过敏、肠易激综合征、哮喘或慢性阻塞性肺疾病等呼吸道疾病、皮肤、眼睛或粘膜刺激、发热、胃十二指肠溃疡、炎症性肠病、炎症性疾病和急性尿失禁。
• Heterocyclic compounds useful as vanilloid receptor antagonists and pharmaceutical compositions containing the same
  申请人：Amorepacific Corporation

  公开号：EP1882687A1

  公开（公告）日：2008-01-30

  This present invention relates to novel compounds, of the formula (I), isomer thereof or pharmaceutically acceptable salts thereof as vanilloid receptor (Vanilloid Receptor 1;VR1;TRPV1) antagonist; and a pharmaceutical composition containing the same. The present invention provides a pharmaceutical composition for preventing or treating a disease such as pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), fecal urgency, gastro-esophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis and pancreatitis.

  这项发明涉及新化合物，其化学式为(I)，其异构体或其药学上可接受的盐作为辣椒素受体（辣椒素受体1; VR1; TRPV1）拮抗剂；以及含有该化合物的药物组合物。本发明提供了一种用于预防或治疗疾病的药物组合物，如疼痛、关节炎炎症性疾病、神经病、艾滋病相关神经病、神经损伤、神经退行性疾病、中风、包括尿失禁、膀胱过敏、膀胱炎、胃十二指肠溃疡、肠易激综合征（IBS）和炎症性肠病（IBD）、粪便紧急情况、胃食管反流病（GERD）、克罗恩病、哮喘、慢性阻塞性肺病、咳嗽、神经症/过敏/炎症性皮肤病、牛皮癣、瘙痒症、疹痒症、皮肤、眼睛或粘膜刺激、听觉过敏、耳鸣、前庭过敏、阵发性眩晕、心脏疾病如心肌缺血、与头发生长有关的疾病如脱发、脱发、鼻炎和胰腺炎。
• 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。
• 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。
• Novel thiourea derivatives and the pharmaceutical compositions containing the same
  申请人：Suh Ger Young

  公开号：US20080064687A1

  公开（公告）日：2008-03-13

  The present invention relates to novel thiourea derivatives as a modulator for vanilloid receptor (VR) and the pharmaceutical compositions containing the same. As diseases associated with the activity of vanilloid receptor, pain acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases.

  本发明涉及一种新型硫脲衍生物，作为vanilloid受体（VR）的调节剂，并包含相应的药物组合物。作为与vanilloid受体活动相关的疾病，可以列举急性疼痛、慢性疼痛、神经病性疼痛、术后疼痛、偏头痛、关节痛、神经病、神经损伤、糖尿病神经病变、神经退行性疾病、神经性皮肤疾病、中风、膀胱过敏、肠易激综合征、哮喘或慢性阻塞性肺疾病、皮肤、眼睛或黏膜刺激、发热、胃十二指肠溃疡、炎症性肠病和炎症性疾病等。本发明提供了一种用于预防或治疗这些疾病的药物组合物。