2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl isothiocyanate | 371248-42-9

• 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: 2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl isothiocyanate
• 英文别名: [2-[(3,4-Dimethylphenyl)methyl]-3-isothiocyanatopropyl] 2,2-dimethylpropanoate
• CAS: 371248-42-9
• 化学式: C₁₈H₂₅NO₂S
• 分子量: 319.468
• InChiKey: JLZAGJVBLBNFMW-UHFFFAOYSA-N

物化性质

• 沸点：
  451.1±45.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl isothiocyanate 在 sodium hydride 、 三氟乙酸 作用下， 生成 2,2-dimethyl-propionic acid 2-[(4-amino-3-methoxy-benzyloxythiocarbonylamino)-methyl]-3-(3,4-dimethyl-phenyl)-propyl ester
  参考文献：
  名称：

  N-（3-酰氧基-2-苄基丙基）-N（'）-[4-（甲基磺酰基氨基）苄基]硫脲类似物作为类香草酸受体拮抗剂的“ B区”的结构活性关系分析：N的发现-羟基硫脲类似物，具有有效的镇痛作用。

  摘要：

  研究了强效和高亲和力类香草醇受体（VR1）铅配体N-（3-酰氧基-2-苄基丙基）-N（'）-[4-（甲基磺酰基氨基）苄基]硫脲在B区的结构修饰。用不同的等排官能团取代硫脲。结构活性分析表明，该系列中的A区是决定激动/拮抗活性的主要因素，而与B区无关。与母体硫脲类似物相比，N（C）-羟基硫脲类似物（12、13）在乙酸扭曲试验中显示出出色的镇痛活性。

  DOI：

  10.1016/j.bmcl.2004.02.002
• 作为产物：
  描述：

  1,1′-硫代羰基二-2(1H)-吡啶酮 、 3-azido-2-(3,4-dimethylbenzyl)propyl pivalate 在 Lindlar's catalyst 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.0h， 以94%的产率得到2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl isothiocyanate
  参考文献：
  名称：

  N-(3-Acyloxy-2-Benzylpropyl)-N′-Dihydroxytetrahydrobenzazepine and Tetrahydroisoquinoline Thiourea Analogues as Vanilloid Receptor Ligands

  摘要：

  The vanilloid receptor represents a promising target for drug development. Building on our previous strategies which have generated potent agonists for VR1, we now describe a series of novel N-(3-acyloxy-2-benzylpropyl)-N'-dihydroxytetrahydro-benzazepine and tetrahydroisoquinoline thiourea analogues, several of which are potent VRI antagonists. We report here the rationale for the design, the synthesis, and the in vitro characterization of activity in assays for [H-3]resiniferatoxin binding and Ca-45 influx using heterologously expressed rat VRI. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00068-2

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。
• <i>N</i>-(3-Acyloxy-2-benzylpropyl)-<i>N</i>‘-[4-(methylsulfonylamino)benzyl]thiourea Analogues:  Novel Potent and High Affinity Antagonists and Partial Antagonists of the Vanilloid Receptor
  作者：Jeewoo Lee、Jiyoun Lee、Myungshim Kang、Myoungyoup Shin、Ji-Min Kim、Sang-Uk Kang、Ju-Ok Lim、Hyun-Kyung Choi、Young-Ger Suh、Hyeung-Geun Park、Uhtaek Oh、Hee-Doo Kim、Young-Ho Park、Hee-Jin Ha、Young-Ho Kim、Attila Toth、Yun Wang、Richard Tran、Larry V. Pearce、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm030089u

  日期：2003.7.1

  Isosteric replacement of the phenolic hydroxyl group in potent vanilloid receptor (VR1) agonists with the alkylsulfonamido group provides a series of compounds which are effective antagonists to the action of the capsaicin on rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells. In particular, compound 61, N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[3-fluoro-4-(methylsulfonylamin

  用烷基磺酰胺基对强效香草醛受体（VR1）激动剂中的酚羟基进行等位置换，提供了一系列化合物，可有效拮抗辣椒素对在中国仓鼠卵巢（CHO）细胞中异源表达的大鼠VR1的作用。特别是，化合物61 N- [2-（3,4-二甲基苄基）-3-新戊酰氧基丙基] -N'-[3-氟-4-（甲基磺酰氨基邻氨基）苄基]硫脲是辣椒素的完全拮抗剂。 K（i）值为7.8 nM（相比之下，卡塞平为520 nM，5-iodoRTX为4 nM），并且在小鼠中显示出出色的镇痛活性。
• Novel thiourea compounds and the pharmaceutical compositions containing the same
  申请人：——

  公开号：US20030212140A1

  公开（公告）日：2003-11-13

  The present invention relates to thiourea compounds and the pharmaceutical compositions containing the same, and particularly, to novel thiourea compounds as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. 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.

  本发明涉及硫脲化合物和含有它们的制药组合物，特别是作为vanilloid受体（VR）拮抗剂的新型硫脲化合物及其制药组合物。作为与vanilloid受体活性相关的疾病，可以列举出疼痛、急性疼痛、慢性疼痛、神经病性疼痛、术后疼痛、偏头痛、关节痛、神经病变、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。本发明提供了一种预防或治疗这些疾病的制药组合物。
• Novel n-hydroxy thiourea, urea and amide compounds and the pharmaceutical compositions comprising the same
  申请人：Lee Jee-Woo

  公开号：US20050288369A1

  公开（公告）日：2005-12-29

  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.

  本发明涉及新型的N-羟基硫脲、尿素和酰胺化合物，作为有效的vanilloid受体拮抗剂及其药物组合物。该创新化合物可用作镇痛药，用于预防、缓解或治疗疼痛疾病或伴随疼痛的炎症性疾病，包括急性疼痛、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、炎症性疾病和紧急尿失禁。
• α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists
  作者：Ho Shin Kim、Mi-Kyoung Jin、Sang-Uk Kang、Ju-Ok Lim、Phuong-Thao Tran、Van-Hai Hoang、Jihyae Ann、Tae-Hwan Ha、Larry V. Pearce、Vladimir A. Pavlyukovets、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1016/j.bmcl.2014.04.054

  日期：2014.6

  A series of alpha-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of alpha-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant. (C) 2014 Elsevier Ltd. All rights reserved.