3-nitro-4-[N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid methyl ester | 259219-18-6

• 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-nitro-4-[N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid methyl ester
• 英文别名: Methyl 3-nitro-4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)amino]benzoate
• CAS: 259219-18-6
• 化学式: C₂₂H₂₆N₂O₄
• 分子量: 382.459
• InChiKey: YMOMBCIDNRKQAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-nitro-4-[N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid methyl ester 在 palladium on activated charcoal 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以94%的产率得到3-amino-4-[N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid methyl ester
  参考文献：
  名称：

  RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without the Side Effects of RXR Full Agonists

  摘要：

  Treating insulin resistance and type 2 diabetes in rodents, currently known retinoid X receptor (RXR) agonists induce significant adverse effects. Here we introduce a novel RXR partial agonist CBt-PMN (11b), which shows a potent glucose-lowering effect and improvements of insulin secretion and glucose tolerance without the serious adverse effects caused by RXR full agonists. We suggest that RXR partial agonists may be a new class of antitype 2 diabetes drug candidates.

  DOI：

  10.1021/ml300055n
• 作为产物：
  描述：

  4-碘苯甲酸 在 氯化亚砜 、 硫酸 、 硝酸 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 甲苯 为溶剂， 反应 11.0h， 生成 3-nitro-4-[N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid methyl ester
  参考文献：
  名称：

  RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without the Side Effects of RXR Full Agonists

  摘要：

  Treating insulin resistance and type 2 diabetes in rodents, currently known retinoid X receptor (RXR) agonists induce significant adverse effects. Here we introduce a novel RXR partial agonist CBt-PMN (11b), which shows a potent glucose-lowering effect and improvements of insulin secretion and glucose tolerance without the serious adverse effects caused by RXR full agonists. We suggest that RXR partial agonists may be a new class of antitype 2 diabetes drug candidates.

  DOI：

  10.1021/ml300055n

文献信息

• Retinoid X Receptor-Antagonistic Diazepinylbenzoic Acids.
  作者：Masayuki EBISAWA、Hiroki UMEMIYA、Kiminori OHTA、Hiroshi FUKASAWA、Emiko KAWACHI、Ghislaine CHRISTOFFEL、Hinrich GRONEMEYER、Motonori TSUJI、Yuichi HASHIMOTO、Koichi SHUDO、Hiroyuki KAGECHIKA

  DOI：10.1248/cpb.47.1778

  日期：——

  Several dibenzodiazepine derivatives were identified as novel retinoid X receptor (RXR) antagonists on the basis of inhibitory activity on retinoid-induced cell differentiation of human promyelocytic leukemia cells HL-60 and transactivation assay using retinoic acid receptors (RARs) and RXRs in COS-1 cells. 4-(5H-2, 3-(2, 5-Di-methyl-2, 5-hexano)-5-n-propyldibenzo[b, e][1, 4]diazepin-11-yl)benzoic acid (HX603, 6c) is an N-n-propyl derivative of an RXR pan-agonist HX600 (6a), and exhibited RXR-selective antagonistic activity. Similar RXR-antagonistic activities were observed with 4-(5H-2, 3-(2, 5-dimethyl-2, 5-hexano)-5-methyl-8-nitrodibenzo[b, e][1, 4]diazepin-11-yl)benzoic acid (HX531, 7a) and 4-(5H-10, 11-dihydro-5, 10-dimethyl-2, 3-(2, 5-dimethyl-2, 5-hexano)-dibenzo[b, e][1, 4]diazepin-11-yl)benzoic acid (HX711, 8b), which also inhibited transactivation of RARs induced by an RAR agonist, Am80. These compounds inhibited HL-60 cell differentiation induced by the combination of a low concentration of the retinoid agonist Am80 with an RXR agonist (a retinoid synergist, HX600). These results indicated that HX603 (6c), and the related RXR antagonists inhibit the activation of RAR-RXR heterodimers as well as RXR homodimers, which is a distinct characteristic different from that of the known RXR antagonist, LG100754 (9).

  根据对视黄醇诱导的人早幼粒细胞白血病细胞 HL-60 的细胞分化的抑制活性，以及利用视黄酸受体（RARs）和 RXRs 在 COS-1 细胞中的转录活化试验，确定了几种二苯并二氮杂卓衍生物为新型视黄酸 X 受体（RXR）拮抗剂。4-(5H-2, 3-(2,5-二甲基-2,5-己酸)-5-正丙基二苯并[b,e][1,4]二氮杂卓-11-基)苯甲酸（HX603，6c）是一种 RXR 泛拮抗剂 HX600（6a）的 N-正丙基衍生物，具有 RXR 选择性拮抗活性。4-(5H-2, 3-(2, 5-dimethyl-2, 5-hexano)-5-methyl-8-nitrodibenzo[b, e][1, 4]diazepin-11-yl)benzoic acid (HX531, 7a) 和 4-(5H-10、11-二氢-5，10-二甲基-2，3-（2，5-二甲基-2，5-己氰基）-二苯并[b，e][1，4]二氮杂卓-11-基)苯甲酸（HX711，8b），它们也能抑制 RAR 激动剂 Am80 诱导的 RARs 的转录活化。这些化合物抑制了低浓度视黄醇激动剂 Am80 与 RXR 激动剂（视黄醇增效剂 HX600）联合诱导的 HL-60 细胞分化。这些结果表明，HX603（6c）和相关的 RXR 拮抗剂能抑制 RAR-RXR 异源二聚体和 RXR 同源二聚体的活化，这是与已知的 RXR 拮抗剂 LG100754（9）不同的显著特点。
• RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without the Side Effects of RXR Full Agonists
  作者：Hiroki Kakuta、Nobumasa Yakushiji、Ryosuke Shinozaki、Fuminori Ohsawa、Shoya Yamada、Yui Ohta、Kohei Kawata、Mariko Nakayama、Manabu Hagaya、Chisa Fujiwara、Makoto Makishima、Shigeyuki Uno、Akihiro Tai、Ami Maehara、Masaru Nakayama、Toshitaka Oohashi、Hiroyuki Yasui、Yutaka Yoshikawa

  DOI：10.1021/ml300055n

  日期：2012.5.10

  Treating insulin resistance and type 2 diabetes in rodents, currently known retinoid X receptor (RXR) agonists induce significant adverse effects. Here we introduce a novel RXR partial agonist CBt-PMN (11b), which shows a potent glucose-lowering effect and improvements of insulin secretion and glucose tolerance without the serious adverse effects caused by RXR full agonists. We suggest that RXR partial agonists may be a new class of antitype 2 diabetes drug candidates.