4-硝基-2-(吡啶-3-基甲基)异吲哚-1,3-二酮 | 152265-43-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 4-硝基-2-(吡啶-3-基甲基)异吲哚-1,3-二酮
• 英文名称: 4-nitro-2-(pyridin-3-ylmethyl)-isoindole-1,3-dione
• 英文别名: 1H-Isoindole-1,3(2H)-dione, 4-nitro-2-(3-pyridinylmethyl)-；4-nitro-2-(pyridin-3-ylmethyl)isoindole-1,3-dione
• CAS: 152265-43-5
• 化学式: C₁₄H₉N₃O₄
• 分子量: 283.243
• InChiKey: XVBVPXQEMMWLKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  96.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-硝基-2-(吡啶-3-基甲基)异吲哚-1,3-二酮 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 4-(tert-butyl)-N-(1,3-dioxo-2-(pyridin-3-ylmethyl)isoindolin-4-yl)benzene sulfonamide
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL AS CCR9 MODULATORS
  [FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS DU CCR9

  摘要：

  公开号：

  WO2015097121A9
• 作为产物：
  描述：

  3-氨甲基吡啶 、 3-硝基邻苯二甲酸酐 以 溶剂黄146 为溶剂， 反应 18.0h， 生成 4-硝基-2-(吡啶-3-基甲基)异吲哚-1,3-二酮
  参考文献：
  名称：

  A New Series of Orally Bioavailable Chemokine Receptor 9 (CCR9) Antagonists; Possible Agents for the Treatment of Inflammatory Bowel Disease

  摘要：

  Chemokine receptor 9 (CCR9), a cell surface chemokine receptor which belongs to the G protein-coupled receptor, 7-trans-membrane superfamily, is expressed on lymphocytes in the circulation and is the key chemokine receptor that enables these cells to target the intestine. It has been proposed that CCR9 antagonism represents a means to prevent the aberrant immune response of inflammatory bowel disease in a localized and disease specific manner and one which is accessible to small molecule approaches. One possible reason why clinical studies with vercirnon, a prototype CCR9 antagonist, were not successful may be due to a relatively poor pharmacokinetic (PK) profile for the molecule. We wish to describe work aimed at producing new, orally active CCR9 antagonists based on the 1,3-dioxoisoindoline skeleton. This study led to a number of compounds that were potent in the nanomolar range and which, on optimization, resulted in several possible preclinical development candidates with excellent PK properties.

  DOI：

  10.1021/acs.jmedchem.5b01840

文献信息

• Benzamide platelet activating factor antagonists
  申请人：Mitsubishi Kasei Corporation

  公开号：US05401756A1

  公开（公告）日：1995-03-28

  Benzamide platelet activating factor antagonists of the following formula (I): ##STR1## wherein ##STR2## B, D: hydrogen atom, etc. E: pyridyl group, etc. n: integer from 0 to 2 R.sup.2 : R.sup.3 R.sup.4 N-- etc. (R.sup.3, R.sup.4 : optionally substituted C.sub.6 -C.sub.12 aryl group, etc.) ##STR3## optical antipodes thereof or pharmaceutically acceptable salts thereof, show excellent PAF antagonism and are effective for therapy and prophylaxis of diseases caused by PAF (bronchial asthma, nephritis, shocks, cardiac infarction, cerebral hemorrhage, ulcer, DIC, autoimmune diseases, thrombosis, etc.).

  苯甲酰胺血小板活化因子拮抗剂的化学式（I）如下：##STR1## 其中，##STR2## B，D：氢原子等。 E：吡啶基等。 n：整数，范围从0到2。 R.sup.2：R.sup.3 R.sup.4 N--等。（R.sup.3，R.sup.4：可选取代的C.sub.6-C.sub.12芳基等） ##STR3## 其光学对映体或药物可接受的盐，表现出优异的PAF拮抗作用，并对由PAF引起的疾病（支气管哮喘、肾炎、休克、心肌梗塞、脑出血、溃疡、DIC、自身免疫疾病、血栓形成等）的治疗和预防具有有效作用。
• Benzamide derivatives
  申请人：Mitsubishi Chemical Corporation

  公开号：EP0548934A1

  公开（公告）日：1993-06-30

  Benzamide derivatives of the following formula (I): [wherein R¹: B, D:hydrogen atom, etc. E:pyridyl group, etc. n:integer from 0 to 2 R²:R³R⁴N- etc. (R³, R⁴: optionally substituted C₆ - C₁₂ aryl group, etc.) A: -CH₂-, -N=H-, -CH=N-, -N=CH-, -CH=CH- or -CH₂-CH₂-]. optical antipodes thereof or pharmaceutically acceptable salts thereof, show excellent PAF antagonism and are effective for therapy and prophylaxis of diseases caused by PAF (bronchial asthma, nephritis, shocks, cardiac infarction, cerebral hemorrhage, ulcer, DIC, autoimmune diseases, thrombosis, etc.).

  下式(I)的苯甲酰胺衍生物： [其中 R¹： B、D:氢原子等 E:吡啶基等 n:0 至 2 的整数 R²:R³R⁴N- 等。 (R³、R⁴：任选取代的 C₆ - C₁₂ 芳基等。） A: -CH₂-、-N=H-、-CH=N-、-N=CH-、-CH=CH-或-CH₂-CH₂-]。 其光学抗原或其药学上可接受的盐类显示出优异的 PAF 拮抗作用，对治疗和预防 PAF 引起的疾病（支气管哮喘、肾炎、休克、心肌梗塞、脑出血、溃疡、DIC、自身免疫性疾病、血栓形成等）有效。
• New anti-inflammatory N-pyridinyl(alkyl)phthalimides acting as tumour necrosis factor-α production inhibitors
  作者：Xavier Collin、Jean-Michel Robert、Gaétane Wielgosz、Guillaume Le Baut、Christine Bobin-Dubigeon、Nicole Grimaud、Jean-Yves Petit

  DOI：10.1016/s0223-5234(01)01254-5

  日期：2001.8

  This paper describes the synthesis of N-pyridinyl(alkyl)phthalimides related to N-phenyl-4,5,6,7-tetrafluorophthalimides known to be inhibitors of tumour necrosis factor-alpha (TNF alpha) production. Pharmacomodulation at the phthalimidic nitrogen led to the selection of two pharmacophoric fragments (2,4-lutidinyl and beta -picolyl), allowing significant inhibition of TNF alpha production (compounds 12 and 17). Variation of the substituents linked to the homocycle of their phthalimide scaffold indicated that high (TNF alpha production) inhibitory potency could be achieved, notably by 5-fluoro, 4- or 5-nitro, 5-amino and especially tetrafluoro substitution. The most active compound, N-(pyridin-3-ylmethyl)-4,5,6,7-tetrafluorophthalimide (32) (84% inhibition at 10 muM), also produced an anti-oedematous effect in the PMA-induced mouse-ear swelling test. Although less active than dexamethasone, it exerted a marked reduction in ear thickness after oral administration (63% vs. 85% for dexamethasone at 0.2 mM kg(-1)) and remained efficient after topical application (46% vs. 96% for the dexamethasone). It also induced potent inhibition in the rat carrageenan foot oedema test with an ID50 (0.14 muM kg(-1)) comparable with that of N-(2,6-diisopropylphenyl)phthalimide (4) (0.15 muM kg(-1)). (C) 2001 Editions scientifiques et medicales Elsevier SAS.
• [EN] COMPOUNDS USEFUL AS CCR9 MODULATORS<br/>[FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS DU CCR9
  申请人：NORGINE BV

  公开号：WO2015097121A9

  公开（公告）日：2015-09-03
• COMPOUNDS USEFUL AS CCR9 MODULATORS
  申请人：Norgine BV

  公开号：EP3087069A1

  公开（公告）日：2016-11-02