2-[3-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxylic acid | 824936-65-4

• 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-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxylic acid
• 英文别名: 1-[3-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxic acid；1-[4-(Methanesulfonamido)-3-methoxyphenyl]cyclopropane-1-carboxylic acid
• CAS: 824936-65-4
• 化学式: C₁₂H₁₅NO₅S
• 分子量: 285.321
• InChiKey: ATXHAEYOMSAPKR-UHFFFAOYSA-N

物化性质

• 沸点：
  488.3±55.0 °C(Predicted)
• 密度：
  1.481±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[3-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxylic acid 在 4 A molecular sieve 、 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

  摘要：

  A series of alpha-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K-i = 41 and 39.2 nM and K-i(ant) = 4.5 and 37 nM). (c) 2007 Published Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.06.041
• 作为产物：
  描述：

  methyl 1-[3-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 2-[3-methoxy-4-(methylsulfonylamino)phenyl]cyclopropanecarboxylic acid
  参考文献：
  名称：

  α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

  摘要：

  A series of alpha-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K-i = 41 and 39.2 nM and K-i(ant) = 4.5 and 37 nM). (c) 2007 Published Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.06.041

文献信息

• [EN] 4-(METHYL SULFONYL AMINO) PHENYL ANALOGUES AS VANILLOID ANTAGONIST SHOWING EXCELLENT ANALGESIC ACTIVITY AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] ANALOGUES DE 4-(METHYL SULFONYL AMINO)PHENYLE UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE AYANT UNE EXCELLENTE ACTIVITE ANALGESIQUE, ET COMPOSITIONS PHARMACEUTIQUE LES COMPRENANT
  申请人：DIGITALBIOTECH CO LTD

  公开号：WO2005003084A1

  公开（公告）日：2005-01-13

  The present invention relates to novel 4-(methylsulfonylamino) phenyl analogue 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.

  本发明涉及一种新型的4-(甲磺胺基)苯基类似物，作为有效的辣椒素受体拮抗剂，以及包含该类似物的药物组合物。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、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、眼睛或粘膜的刺激、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。
• 4-(Methyl sulfonyl amino) phenyl analogues as vanilloid antagonist showing excellent analgesic activity and the pharmaceutical compositions comprising the same
  申请人：Lee Woo Jee

  公开号：US20060258884A1

  公开（公告）日：2006-11-16

  4-(methylsulfonylamino)phenyl analogues as potent vanilloid receptor antagonists and pharmaceutical compositions comprising the same. The compounds are useful as analgesics to prevent, alleviate or treat pain diseases or inflammatory disease including 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.

  4-(甲基磺酰氨基)苯类似物作为有效的vanilloid受体拮抗剂和包含它们的制药组合物。这些化合物可用作镇痛剂，以预防、缓解或治疗疼痛疾病或炎症性疾病，包括疼痛、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、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、呼吸系统疾病，如哮喘或慢性阻塞性肺病、皮肤、眼睛或黏膜刺激、发热、胃十二指肠溃疡、炎症性肠病、炎症性疾病和紧急的尿失禁。
• Stereospecific High-affinity TRPV1 Antagonists: Chiral <i>N</i>-(2-Benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues
  作者：HyungChul Ryu、Mi-Kyoung Jin、Su Yeon Kim、Hyun-Kyung Choi、Sang-Uk Kang、Dong Wook Kang、Jeewoo Lee、Larry V. Pearce、Vladimir A. Pavlyukovets、Matthew A. Morgan、Richard Tran、Attila Toth、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm701049p

  日期：2008.1.1

  Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.
• 2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure–activity relationships in the B and C-regions
  作者：Wei Sun、Keliang Liu、HyungChul Ryu、Dong Wook Kang、Yong Soo Kim、Myeong Seop Kim、Yongsung Cho、Rahul S. Bhondwe、Shivaji A. Thorat、Ho Shin Kim、Larry V. Pearce、Vladimir A. Pavlyukovets、Richard Tran、Matthew A. Morgan、Jozsef Lazar、Christopher B. Ryder、Attila Toth、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1016/j.bmc.2011.12.014

  日期：2012.2

  On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure-activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K-i = 21.5 nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K-i(ant) = 8.0 nM comparable to 3. (C) 2011 Elsevier Ltd. All rights reserved.
• 4-(METHYL SULFONYL AMINO) PHENYL ANALOGUES AS VANILLOID ANTAGONIST SHOWING EXCELLENT ANALGESIC ACTIVITY AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：Grünenthal GmbH

  公开号：EP1658265A1

  公开（公告）日：2006-05-24