KMJ-518

• 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: KMJ-518
• 英文别名: N-[3-(4-chloro-phenyl)-propyl]-2-(3-fluoro-4-methanesulfonylamino-phenyl)-propionamide；N-[3-(4-chlorophenyl)propyl]-2-[3-fluoro-4-(methylsulfonylamino)phenyl]propionamide；N-[3-(4-chlorophenyl)propyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide
• 化学式: C₁₉H₂₂ClFN₂O₃S
• 分子量: 412.913
• InChiKey: BMBZWMQGQVEOCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(3-fluoro-4-methylsulfonylaminophenyl)propionic acid 、 3-(4-氯苯基)-丙胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以70%的产率得到KMJ-518
  参考文献：
  名称：

  2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure–activity relationships in the B and C-regions

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.12.014

文献信息

• 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。
• US8642657B2
  申请人：——

  公开号：US8642657B2

  公开（公告）日：2014-02-04
• 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.