2-[N-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtalen-2-yl)amino]pyrimidine-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-[N-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtalen-2-yl)amino]pyrimidine-5-carboxylic acid
• 英文别名: 2-[Propyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)amino]pyrimidine-5-carboxylic acid
• 化学式: C₂₂H₂₉N₃O₂
• 分子量: 367.491
• InChiKey: PSBKDHRKBKHTGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二叔丁基苯胺 在 氢氧化钾 、 sodium hydride 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[N-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtalen-2-yl)amino]pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  PYRIMIDINE CARBOXYLIC ACID DERIVATIVES

  摘要：

  公开号：

  EP1180520B1

文献信息

• Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids.
  作者：Kiminori OHTA、Emiko KAWACHI、Noriko INOUE、Hiroshi FUKASAWA、Yuichi HASHIMOTO、Akiko ITAI、Hiroyuki KAGECHIKA

  DOI：10.1248/cpb.48.1504

  日期：——

  Several pyridine-and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid (2b) and 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)amino]pyrimidene-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

  几种吡啶和嘧啶羧酸被合成为视黄酸核受体、视黄酸受体（RARs）和视黄酸X受体（RXRs）的配体候选物。虽然吡啶衍生物，6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基甲酰]吡啶-3-羧酸（2b）和6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)羧酰胺]吡啶-3-羧酸（5b）比相应的苯甲酸型视黄酸更有效，如Am80（2a）和Am580（5a），但将Am580（5a）、Am555（6a）或Am55（7a）的苯环替换为嘧啶环会导致视黄酸活性在HL-60细胞分化试验和使用COS-1细胞的RAR转录激活试验中丧失。另一方面，具有二苯胺骨架（DA系列，8和9）的强效RXR激动剂（视黄酸协同剂）的嘧啶类似物（PA系列，10和11）在HL-60细胞分化试验中表现出强效的视黄酸协同活性并激活RXRs。在合成的化合物中，2-[N-正丙基-N-(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基]嘧啶-5-羧酸（PA013，10e）在HL-60试验中是最活跃的视黄酸协同剂。
• HETEROCYCLIC CARBOXYLIC ACID DERIVATIVES
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：EP1180520A1

  公开（公告）日：2002-02-20

  Compounds or salts thereof represented by the formula (I) wherein R1 represents hydrogen atom, a C1-6 alkyl group, a C1-6 alkenyl group, or an acyl group, R2 and R3 represent hydrogen atom or a C1-6 alkyl group, or adjacent R2 and R3 may combine to form 5- to 7-membered ring, R4 represents hydrogen atom, hydroxyl group, a C1-6 alkoxyl group, a C1-6 alkyl group, HAr represents a heteroaryl-diyl group consisting of a 5-membered or 6-membered ring containing 1 to 3 hetero atoms, R5 represents hydrogen atom or a C1-6 alkyl group. The compounds or the salts thereof have retinoid-like physiological activities or controlling activity on physiological activities of retinoid.

  由式(I)代表的化合物或其盐 其中 R1 代表氢原子、C1-6 烷基、C1-6 烯基或酰基，R2 和 R3 代表氢原子或 C1-6 烷基，或相邻的 R2 和 R3 可结合形成 5 至 7 元环、R4 代表氢原子、羟基、C1-6 烷氧基、C1-6 烷基，HAr 代表杂芳基二基，由含有 1 至 3 个杂原子的 5 元环或 6 元环组成，R5 代表氢原子或 C1-6 烷基。这些化合物或其盐类具有类似视黄醇的生理活性或控制视黄醇生理活性的活性。
• Method for treating cachexia with retinoid ligands
  申请人：Jiang Guang Liang

  公开号：US20070185055A1

  公开（公告）日：2007-08-09

  The present invention relates to a method of treatment of cachexia in a subject in need of treatment. More specifically, the present invention relates to the use of retinoid compounds that act on retinoid X receptors (RXRs) for the treatment of cachexia in a subject in need of treatment. The cachexia is associated with, in other words a complication of, a primary disease, condition or disorder. Primary diseases, conditions and disorders include, but are not limited to, cancer, AIDS, liver cirrhosis, diabetes mellitus, chronic renal failure, chronic obstructive pulmonary disease, chronic cardiac failure, immune system diseases (e.g., rheumatoid arthritis and systemic lupus erythematosus), tuberculosis, cystic fibrosis, gastrointestinal disorders (e.g., irritable bowel syndrome and inflammatory bowel disease), Parkinson's disease, anorexia nervosa, dementia, major depression, an aged condition and sarcopenia.
• PYRIMIDINE CARBOXYLIC ACID DERIVATIVES
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：EP1180520B1

  公开（公告）日：2007-06-20