1-(4-((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester | 502433-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(4-((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester
• 英文别名: benzyl 2-[2-methyl-1-[4-[[(2S)-4-methyl-2,3-dihydro-1,4-benzoxazin-2-yl]methoxy]benzoyl]indol-4-yl]acetate
• CAS: 502433-34-3
• 化学式: C₃₅H₃₂N₂O₅
• 分子量: 560.649
• InChiKey: OWCLKNDEPUVPED-LJAQVGFWSA-N

物化性质

• 沸点：
  685.7±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 、 异丙醇 为溶剂， 生成 1-(4-((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid
  参考文献：
  名称：

  Discovery of orally active prostaglandin D2 receptor antagonists

  摘要：

  A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D-2 (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.039
• 作为产物：
  描述：

  2-methyl-1H-indol-4-yl trifluoromethanesulfonate 在 TEA 四氢吡咯 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 copper(l) iodide 、 bis(cyclohexanyl)borane 、 四丁基氯化铵 、 四丁基碘化铵 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1-(4-((2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethoxy)benzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester
  参考文献：
  名称：

  Discovery of orally active prostaglandin D2 receptor antagonists

  摘要：

  A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D-2 (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.039

文献信息

• Indole derivatives, process for producing the same and drugs containing the same as the active ingredient
  申请人：Torisu Kazuhiko

  公开号：US20050004096A1

  公开（公告）日：2005-01-06

  Indole derivatives represented by formula (I) wherein all symbols represent the same as that in specification), production methods thereof, and DP receptor antagonist comprising them as active ingredients. Since the compounds of formula (I) binds and antagonizes to DP receptor, they are useful for the prevention and/or treatment against allergic diseases, diseases accompanied with itching, secondary diseases generated by behaviors caused by itching, inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis.

  公式（I）所表示的吲哚衍生物（其中所有符号均与规范中相同），其生产方法以及包含它们作为活性成分的DP受体拮抗剂。由于公式（I）中的化合物结合并拮抗DP受体，因此它们对于预防和/或治疗过敏性疾病、伴随瘙痒的疾病、由瘙痒引起的行为所致的继发疾病、炎症、慢性阻塞性肺疾病、缺血再灌注障碍、脑血管疾病、风湿性关节炎并发的胸膜炎、溃疡性结肠炎等具有用处。
• INDOLE DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1424325A1

  公开（公告）日：2004-06-02

  Indole derivatives represented by formula (I)    wherein all symbols represent the same as that in specification), production methods thereof, and DP receptor antagonist comprising them as active ingredients. Since the compounds of formula (I) binds and antagonizes to DP receptor, they are useful for the prevention and/or treatment against allergic diseases, diseases accompanied with itching, secondary diseases generated by behaviors caused by itching, inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis.

  由式（I）代表的吲哚衍生物 其中所有符号均与说明书中的符号相同）的吲哚衍生物、其生产方法以及以它们为活性成分的 DP 受体拮抗剂。 由于式（I）化合物能结合并拮抗 DP 受体，因此可用于预防和/或治疗过敏性疾病、伴随瘙痒的疾病、由瘙痒引起的行为所导致的继发性疾病、炎症、慢性阻塞性肺病、缺血性再灌注疾病、脑血管疾病、类风湿性关节炎并发的胸膜炎、溃疡性结肠炎。
• METHODS AND COMPOSITIONS FOR INHIBITING OR REDUCING HAIR LOSS
  申请人：The Trustees of the University of Pennsylvania

  公开号：EP3175856A1

  公开（公告）日：2017-06-07

  A non-therapeutic method of treating baldness in the scalp of a subject, the method comprising administering a prostaglandin D2 receptor (DP receptor) antagonist to the subject. The antagonist may be a prostaglandin D2 receptor 2 (DP2 receptor) antagonist.

  一种治疗受试者头皮秃发的非治疗方法，该方法包括向受试者施用前列腺素 D2 受体（DP 受体）拮抗剂。拮抗剂可以是前列腺素D2受体2（DP2受体）拮抗剂。
• Methods and compositions for inhibiting or reducing hair loss, acne, rosacea, prostate cancer, and BPH
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US10849841B2

  公开（公告）日：2020-12-01

  This invention provides methods of treating androgenetic alopecia (AGA), acne, rosacea, prostate cancer, and benign prostatic hypertrophy (BPH), comprising the step of contacting a subject with a compound or composition capable of decreasing prostaglandin D2 (PGD2) level or activity, a downstream signaling or receptor pathway thereof, or prostaglandin D2 synthase level or activity; methods of stimulating hair growth, comprising the step of contacting a subject with a compound or composition capable of increasing or decreasing the activity or level of a target gene of the present invention, or with a protein product of the target gene or an analogue or mimetic thereof; and methods of testing for AGA and evaluating therapeutic methods thereof, comprising measuring PGD2 levels.

  本发明提供了治疗雄激素性脱发(AGA)、痤疮、酒渣鼻、前列腺癌和良性前列腺肥大(BPH)的方法，包括使受试者与能降低前列腺素D2(PGD2)水平或活性、其下游信号传导或受体通路或前列腺素D2合成酶水平或活性的化合物或组合物接触的步骤；刺激毛发生长的方法，包括使受试者接触能提高或降低本发明靶基因活性或水平的化合物或组合物，或接触靶基因的蛋白产物或其类似物或模拟物；以及检测 AGA 和评估其治疗方法的方法，包括测量 PGD2 水平。
• EP1424325
  申请人：——

  公开号：——

  公开（公告）日：——