7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-nitro-1H-quinolin-2-one | 199861-68-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-nitro-1H-quinolin-2-one
• CAS: 199861-68-2
• 化学式: C₁₇H₁₃ClN₂O₄
• 分子量: 344.754
• InChiKey: BHXCYYJAKSKFGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-nitro-1H-quinolin-2-one 在 三苯基膦 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (S)-2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Antagonists of gonadotropin releasing hormone

  摘要：

  公式（I）的化合物及其药用盐被披露，可用作GnRH拮抗剂，因此可能对多种与性激素相关的疾病的治疗有用。

  公开号：

  US06147088A1
• 作为产物：
  描述：

  甲基2-胺-4-氯苯酚酯 在 硫酸 、 硝酸 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 生成 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-nitro-1H-quinolin-2-one
  参考文献：
  名称：

  Quinolones as gonadotropin releasing hormone (GnRH) antagonists: simultaneous optimization of the C(3)-aryl and C(6)-substituents

  摘要：

  A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to he optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00318-8

文献信息

• Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists
  作者：Robert J. DeVita、Mark T. Goulet、Matthew J. Wyvratt、Michael H. Fisher、Jane-L. Lo、Yi Tien Yang、Kang Cheng、Roy G. Smith

  DOI：10.1016/s0960-894x(99)00447-3

  日期：1999.9

  appropriate cyclic D- or L-amino acids by the Amdt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines

  报道了喹诺酮GnRH拮抗剂（+/-）-1对映体的合成和体外活性。由适当的环状D-或L-氨基酸，通过Amdt-Eistert同系反应，然后还原所得酯，制备手性氨基醇。这些药效基团的掺入是通过4-羟基喹诺酮类的新Mitsunobu烷基化实现的。与大鼠GnRH受体结合的关键胺药效团在S构型中最活跃。环的大小对于效能而言并不重要，其中4、5、6和7元环胺表现出相似的效能。
• Syntheses and structure–activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists
  作者：Jinlong Jiang、Robert J. DeVita、Mark T. Goulet、Matthew J. Wyvratt、Jane-L. Lo、Ning Ren、Joel B. Yudkovitz、Jisong Cui、Yi T. Yang、Kang Cheng、Susan P. Rohrer

  DOI：10.1016/j.bmcl.2003.12.101

  日期：2004.4

  Syntheses and structure-activity relationships of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists are described. Some of substituents on the piperidine ring that were investigated included a fused phenyl group, a (6R)-trifluoromethyl group, (6S) and (6R)-methyl group. This study showed that GnRH binding potency was tolerated by a small group at the 6-position of the piperidine, and blocking the 6-position by a trifluoromethyl group reduced clearance rate and increased oral bioavailability. (C) 2004 Elsevier Ltd. All rights reserved.
• Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist
  作者：Robert J. DeVita、Darius D. Hollings、Mark T. Goulet、Matthew J. Wyvratt、Michael H. Fisher、Jane-L. Lo、Yi Tien Yang、Kang Cheng、Roy G. Smith

  DOI：10.1016/s0960-894x(99)00446-1

  日期：1999.9

  Screening of the Merck sample collection for non-peptide compounds with binding affinity for the rat GnRH receptor led to the identification of the substituted quinolone (1) as a lead compound in the search for a non-peptide GnRH receptor antagonist. Substantial improvements in potency (similar to 300 fold) were achieved by addition of an alkyl amine at the 4-position, a 3,5-dimethylphenyl group at the 3-position and 6-nitro-7-chloro-substitution of the 1H-quinolone core. (C) 1999 Elsevier Science Ltd. All rights reserved.
• ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE
  申请人：MERCK & CO., INC.

  公开号：EP0901471A1

  公开（公告）日：1999-03-17
• EP0901471A4
  申请人：——

  公开号：EP0901471A4

  公开（公告）日：1999-08-25