5-thia-16-(3-methoxymethylphenyl)methylPGE1 | 256382-23-7

• 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: 5-thia-16-(3-methoxymethylphenyl)methylPGE1
• 英文别名: 4-{[2-((1R,2R,3R)-3-hydroxy-2-{(1E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-5-oxocyclopentyl)ethyl]sulfanyl}butanoic acid；(11α,13E,15α)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid；(11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid；Ono-AE1-437；4-[2-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl]-5-oxocyclopentyl]ethylsulfanyl]butanoic acid
• CAS: 256382-23-7
• 化学式: C₂₃H₃₂O₆S
• 分子量: 436.569
• InChiKey: ORSJUPRAHPZYRL-XHTUOEPPSA-N

物化性质

• 沸点：
  635.2±55.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-辛基单氧乙烯 、 5-thia-16-(3-methoxymethylphenyl)methylPGE1 在 1H-benzotriazol-1-yl methanesulfonate 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 生成 (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-octyloxyethyl ester
  参考文献：
  名称：

  REMEDIES FOR DISEASES WITH BONE MASS LOSS HAVING EP4 AGONIST AS THE ACTIVE INGREDIENT

  摘要：

  公开号：

  EP1417975B1
• 作为产物：
  描述：

  甲基4-({2-[(1R,2R,3S)-3-羟基-2-{(1E)-3-羟基-4-[3-(甲氧基甲基)苯基]-1-丁烯-1-基}-5-氧代环戊基]乙基}硫基)丁酸酯 在 porcine liver esterase 作用下， 以 phosphate buffer 、 二甲基亚砜 为溶剂， 反应 1.0h， 以85%的产率得到5-thia-16-(3-methoxymethylphenyl)methylPGE1
  参考文献：
  名称：

  Design and synthesis of a selective EP4-receptor agonist. Part 3: 16-phenyl-5-thiaPGE1 and 9-β-halo derivatives with improved stability

  摘要：

  To identify a new selective EP4-agonist with improved chemical stability, further chemical modification of those reported previously was continued. We focused our attention on chemical modification of the alpha chain of 3,7-dithiaPGE(1), and selected 5-thiaPGE(1), as a new chemical lead, Introduction of an optimized omega to chain to the 5-thiaPG skeleton afforded in-methoxymethyl derivative 33a, which showed the most potent EP4-receptor agonist activity and good subtype-selectivity both in vitro and in vivo. 9beta-HaloPGF derivatives were also synthesized and biologically evaluated in an attempt to block self-degradation of the beta-hydroxyketone moiety. Among these series, 39a and 39b showed potent agonist activity and good subtype-selectivity. Structure-activity relationships (SARs) are also discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00031-7

文献信息

• PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DISEASES ASSOCIATED WITH DECREASE IN BONE MASS COMPRISING EP4 AGONIST AS ACTIVE INGREDIENT
  申请人：MARUYAMA Toru

  公开号：US20100010222A1

  公开（公告）日：2010-01-14

  A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP 4 agonist as an active ingredient. An EP 4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).

  一种用于局部治疗预防和/或治疗与骨量减少相关疾病的药物组合物，包括EP4激动剂作为活性成分。EP4激动剂，其中包括具有前列腺素骨架的化合物作为代表，具有促进骨形成的作用，因此对于预防和/或治疗与骨量减少相关的疾病（如原发性骨质疏松症、继发性骨质疏松症、骨癌转移、高钙血症、帕吉特病、骨丢失和骨坏死、术后骨生成、骨移植替代疗法）非常有用。
• PREVENTIVE AND/OR REMEDY FOR LOWER URINARY TRACT DISEASES CONTAINING EP4 AGONIST
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1782830A1

  公开（公告）日：2007-05-09

  A preventive and/or a remedy for lower urinary tract diseases such as inflammation in the lower urinary tract, cystitis (interstitial cystitis, etc.) and urethritis; (2) an agent for improving bladder compliance and/or bladder capacity; and (3) an agent for protecting bladder mucosa and/or bladder epithelial cells and/or promoting the regeneration thereof; each containing an EP4 agonist. An EP4 agonist is useful in ameliorating symptoms of lower urinary tract diseases such as (1) frequent urination, (2) urgency of urination, (3) pain in the reproductive organs and/or lower urinary tract (for example, bladder pain, urinary tract pain, vulvar pain, vaginal pain, scrotal pain, perineal pain, pelvic pain, etc.) and/or (4) discomfort in the reproductive organs and/or lower urinary tract. Among all, a selective EP4 agonist is useful as a preventive and/or remedy for lower urinary tract diseases having no side effect.

  一种预防和/或治疗下尿路疾病，如下尿路炎症、膀胱炎（间质性膀胱炎等）和尿道炎的制剂；(2) 一种改善膀胱顺应性和/或膀胱容量的制剂；(3) 一种保护膀胱粘膜和/或膀胱上皮细胞和/或促进其再生的制剂；每种制剂都含有一种EP4激动剂。 EP4 激动剂可用于改善下尿路疾病的症状，如(1) 尿频，(2) 尿急，(3) 生殖器官和/或下尿路疼痛（例如，膀胱痛、尿道痛、外阴痛、阴道痛、阴囊痛、会阴痛、骨盆痛等）和/或(4) 生殖器官和/或下尿路不适。其中，选择性 EP4 激动剂可用于预防和/或治疗下尿路疾病，且无副作用。
• TRENADERMAL ABSORPTION PREPARATION
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1878429A1

  公开（公告）日：2008-01-16

  The present invention relates to a blood concentration regulation type percutaneous absorption preparation, which comprises an ester form of 4-[2-((1R,2R,3R)-3-hydroxy-2-(1E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-l-enyl}-5- oxocyclopentyl)ethyl]sulfanyl}butanoic acid and a base for external preparations. The blood concentration regulation type percutaneous absorption preparation of the present invention can stably maintain blood concentration of the active form of the present invention and is safe since there are no side effects. Therefore, it can be used as a percutaneous absorption preparation which can be persistently administered.

  本发明涉及一种血液浓度调节型经皮吸收制剂，它包括 4-[2-((1R,2R,3R)-3-羟基-2-(1E,3S)-3-羟基-4-[3-(甲氧基甲基)苯基]丁-烯基}-5-氧代环戊基)乙基]硫烷基}丁酸的酯型和一种外用制剂基质。本发明的血药浓度调节型经皮吸收制剂可以稳定地维持本发明活性物质的血药浓度，并且由于没有副作用，所以是安全的。因此，本发明可用作可持续给药的经皮吸收制剂。
• ADHESIVE PREPARATION
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2085088A1

  公开（公告）日：2009-08-05

  An adhesive preparation which has a pressure-sensitive adhesive layer comprising two components, i.e., a C1-4 alcohol ester of 4-[2-((1R,2R,3R)-3-hydroxy-2-(1E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-5-osocyclopentyl)ethyl]sulfanyl}butanoic acid and a silicone-based pressure-sensitive adhesive. This is an effective and safe preparation which is stable, shows little change in skin permability and release a drug not rapidly but continuously.

  一种粘合剂制剂，其压敏粘合层由两种成分组成，即 4-[2-((1R,2R,3R)-3-羟基-2-(1E,3S)-3-羟基-4-[3-(甲氧基甲基)苯基]丁-1-烯基}-5-氧代环戊基)乙基]硫甲基}丁酸的 C1-4 醇酯和硅基压敏粘合剂。这是一种有效而安全的制剂，其性质稳定，对皮肤的耐受性几乎没有变化，并能迅速而持续地释放药物。
• CYTOTOXIC T CELL ACTIVATOR COMPRISING EP4 AGONIST
  申请人：Nat. University Corp. Hamamatsu University School of Medicine

  公开号：EP2147672A1

  公开（公告）日：2010-01-27

  Disclosed is a substance which has a low molecular weight, can be applied in a simpler manner, and has an immnopotentiating activity against cancer and/or a microorganism-mediated infectious disease. An EP4 agonist exhibits an immunopotentiating activity through the activation of a cytotoxic T cell, and is therefore useful for the prevention and/or treatment of cancer or a microorganism-mediated infection disease.

  本发明公开了一种分子量低、应用方式简单、对癌症和/或微生物介导的感染性疾病具有免疫增强活性的物质。 EP4 激动剂通过激活细胞毒性 T 细胞而表现出免疫增强活性，因此可用于预防和/或治疗癌症或微生物介导的感染性疾病。