3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-5-dimethylphenoxymethyl]benzoic acid | 459841-26-0

• 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: 3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-5-dimethylphenoxymethyl]benzoic acid
• 英文别名: 3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic acid；4-[[4,5-dimethyl-2-[(5-methylfuran-2-yl)sulfonyl-(2-methylpropyl)amino]phenoxy]methyl]-3-methylbenzoic acid
• CAS: 459841-26-0
• 化学式: C₂₆H₃₁NO₆S
• 分子量: 485.601
• InChiKey: IQXOMZMFCPBOBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-5-dimethylphenoxymethyl]benzoic acid 在 N,N-二甲基甲酰胺 草酰氯 、 氨 、 三氟甲磺酸 作用下， 以 二氯甲烷 、 水 、 吡啶 为溶剂， 反应 1.91h， 生成 N-[4,5-dimethyl-2-(2-methyl-4-cyanophenylmethyloxy)phenyl]-N-isobutyl-(5-methyl-2-furyl) sulfonylamide
  参考文献：
  名称：

  N-PHENYLARYLSULFONAMIDE COMPOUND, DRUG CONTAINING THE COMPOUND AS ACTIVE INGREDIENT, INTERMEDIATE FOR THE COMPOUND, AND PROCESSES FOR PRODUCING THE SAME

  摘要：

  公开号：

  EP1369419B1
• 作为产物：
  描述：

  4-溴-2-甲基苯甲酸 在 palladium diacetate 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 三溴化磷 、 铁粉 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 二甲胺 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.17h， 生成 3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-5-dimethylphenoxymethyl]benzoic acid
  参考文献：
  名称：

  Optimization of sulfonamide derivatives as highly selective EP1 receptor antagonists

  摘要：

  A series of 4-[(2-{isobutyl[(5-methyl-2-furyl)sulfonyl]amino}phenoxy)methyl]benzoic acids and 4-({2-[isobutyl(1,3-thiazol-2-ylsulfonyl)amino]phenoxy}methyl)benzoic acids were synthesized and evaluated for their EP receptor affinities and EP1 receptor antagonist activities. Further structural optimization was carried out to reduce inhibitory activity against hepatic cytochrome P450 isozymes, which could represent a harmful potential drug interaction. Selected compounds were also evaluated for their binding affinities to hTP, hDP, mFP, and hIP, and for their hEP1 receptor antagonist activities. The results of structure-activity relationship studies are also presented.

  DOI：

  10.1016/j.bmc.2006.08.001

文献信息

• Novel pharmaceutical compounds
  申请人：Tung Roger

  公开号：US20070037815A1

  公开（公告）日：2007-02-15

  The present invention relates to derivatives of tadalafil, substituted with fluorine on the methylene carbon atom situated between the oxygens of the benzodioxol ring, and optionally further substituted with deuterium atoms in place of normally abundant hydrogen, and 13 C in place of normally abundant 12 C. These compounds are selective PDE5 inhibitors and possess advantageous biopharmaceutical and pharmacokinetic properties. The invention further provides compositions comprising these compounds and methods of treating diseases and conditions that are responsive to PDE5 inhibition, alone and in combination with additional agents.

  本发明涉及替代他达拉非的衍生物，在苯并二氧杂环戊二烷环的氧原子之间的亚甲基碳原子上取代氟，并且可选地进一步用氘原子取代正常丰富的氢，以及用13C取代正常丰富的12C。这些化合物是选择性的PDE5抑制剂，并具有有利的生物制药和药代动力学性质。该发明还提供了包含这些化合物的组合物和治疗对PDE5抑制有响应的疾病和症状的方法，单独或与其他药物联合使用。
• Remedies for depression containing ep1 antagonist as the active ingredient
  申请人：——

  公开号：US20040082653A1

  公开（公告）日：2004-04-29

  A pharmaceutical composition for the treatment and/or prevention of depression comprising a compound having an antagonistic activity for EP 1 receptor which a prostaglandin E 2 receptor subtype. EP 1 antagonist is useful for the treatment of depression, for example, endogenous depression, reactive depression, weatherability depression, neurological depressed state, the depressed state of brain organic mental disorder.

  一种用于治疗和/或预防抑郁症的药物组合物，包括一种具有EP1受体拮抗活性的化合物，该受体是前列腺素E2受体亚型。EP1拮抗剂对于治疗抑郁症很有用，例如内源性抑郁症，反应性抑郁症，耐受性抑郁症，神经学抑郁状态，脑器质性心境障碍的抑郁状态。
• N-phenylarylsulfonamide compound drug containing the compound as active ingredient intermediate for the compound and processes for producing the same
  申请人：Naganawa Atsushi

  公开号：US20050124672A1

  公开（公告）日：2005-06-09

  An N-phenylarylsulfonylamide compound of formula (I) (R 1 is COOH etc.; R 2 is hydrogen, methyl, etc.; R 3 and R 4 are a combination of methyl and methyl, etc.; R 5 is isopropyl etc.; Ar is thiazolyl, pyridyl, 5-methyl-2-furyl each optionally substituted with methyl; n is zero or 1), a synthetic intermediate for the compound and a process for its preparation. The compound of formula (I) binds to a prostaglandin E 2 receptor, especially an EP 1 subtype receptor, and antagonizes it. It is less affected by protein binding, so it has a satisfactory in vivo activity. Therefore, it is considered to be useful as an analgesic, an antipyretic agent, an agent for the treatment of pollakiuria (frequent urination) and/or lower urinary tract disease syndrome or an antineoplastic agent.

  化合物的化学式为(I)，其中N-苯基磺酰胺化合物（R1为COOH等；R2为氢，甲基等；R3和R4为甲基和甲基的组合等；R5为异丙基等；Ar为噻唑基，吡啶基，5-甲基-2-呋喃基，每个基团可选地取代甲基；n为零或1），是该化合物的合成中间体，以及其制备方法。化合物(I)与前列腺素E2受体结合，特别是EP1亚型受体，并拮抗它。它受蛋白结合的影响较小，因此具有令人满意的体内活性。因此，它被认为是一种有用的镇痛剂，退热剂，治疗频尿和/或下尿路疾病综合征或抗肿瘤剂的药物。
• N-phenylarylsulfonamide compound, pharmaceutical composition comprising the compound as active ingredient, synthetic intermediate for the compound and process for its preparation
  申请人：Naganawa Atsushi

  公开号：US20060030713A1

  公开（公告）日：2006-02-09

  An N-phenylarylsulfonylamide compound of formula (I) (R 1 is COOH etc.; R 2 is hydrogen, methyl, etc.; R 3 and R 4 are a combination of methyl and methyl, etc.; R 5 is isopropyl etc.; Ar is thiazolyl, pyridyl, 5-methyl-2-furyl each optionally substituted with methyl; n is zero or 1), a synthetic intermediate for the compound and a process for its preparation. The compound of formula (I) binds to a prostaglandin E 2 receptor, especially an EP 1 subtype receptor, and antagonizes it. It is less affected by protein binding, so it has a satisfactory in vivo activity. Therefore, it is considered to be useful as an analgesic, an antipyretic agent, an agent for the treatment of pollakiuria (frequent urination) and/or lower urinary tract disease syndrome or an antineoplastic agent.

  公式（I）的N-苯基磺酰胺化合物（其中R1为COOH等；R2为氢，甲基等；R3和R4为甲基和甲基的组合等；R5为异丙基等；Ar为噻唑基，吡啶基，5-甲基-2-呋喃基，每个都可以选择性地用甲基取代；n为零或1），用于该化合物的合成中间体以及其制备方法。公式（I）的化合物结合到前列腺素E2受体，特别是EP1亚型受体，并对其产生拮抗作用。它受蛋白结合的影响较小，因此具有令人满意的体内活性。因此，它被认为是一种有用的镇痛剂，退烧剂，治疗排尿频繁和/或下尿路疾病综合征或抗肿瘤剂的药物。
• Remedies for depression containing EP1 antagonist as the active ingredient
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US07335776B2

  公开（公告）日：2008-02-26

  A pharmaceutical composition for the treatment and/or prevention of depression comprising a compound having an antagonistic activity for EP1 receptor which a prostaglandin E2 receptor subtype. EP1 antagonist is useful for the treatment of depression, for example, endogenous depression, reactive depression, weatherability depression, neurological depressed state, the depressed state of brain organic mental disorder.

  一种用于治疗和/或预防抑郁症的药物组合物，包括一种具有对EP1受体拮抗活性的化合物，该受体是前列腺素E2受体亚型。EP1拮抗剂对于治疗抑郁症是有用的，例如内源性抑郁症，反应性抑郁症，气候适应性抑郁症，神经系统抑郁状态，脑器质性精神障碍的抑郁状态。