(4-甲氧基苯基)(吡啶-3-基)甲醇 | 89667-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: (4-甲氧基苯基)(吡啶-3-基)甲醇
• 英文名称: (4-methoxyphenyl)(pyridine-3-yl)methanol
• 英文别名: (4-methoxyphenyl)(pyridin-3-yl)methanol；(4-methoxyphenyl)(pyridin-3-y)methanol；(4-methoxyphenyl)pyridin-3-yl-methanol；(4-methoxyphenyl)(3-pyridyl)methanol；pyridin-3-yl-4-methoxyphenylcarbinol；3-pyridyl-4-methoxyphenylcarbinol；(4-methoxyphenyl)-pyridin-3-ylmethanol
• CAS: 89667-06-1
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: LUJXIFUKAWFOTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-甲氧基苯基)(吡啶-3-基)甲醇 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 4-甲氧基苯基(3-吡啶基)甲酮
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005
• 作为产物：
  描述：

  3-溴吡啶 、 4-甲氧基苯甲醛 在 正丁基锂 作用下， 生成 (4-甲氧基苯基)(吡啶-3-基)甲醇
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005

文献信息

• METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt
  申请人：Janssen Pharmaceutica NV

  公开号：US20150105366A1

  公开（公告）日：2015-04-16

  The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

  本发明包括式I的化合物。 其中： R1、R2、R3、R4、R5、R6、R7、R8和R9在说明书中定义。 本发明还包括治疗或改善综合征、紊乱或疾病的方法，其中所述综合征、紊乱或疾病为类风湿性关节炎或银屑病。本发明还包括通过给予治疗有效量的至少一个权利要求1的化合物，来调节哺乳动物中RORγt活性的方法。
• [EN] METHYLENE LINKED QUINOLINYL MODULATORS OF ROR-GAMMA-T<br/>[FR] MODULATEURS QUINOLINYLE À LIAISON MÉTHYLÈNE DE ROR-GAMMA-T
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2015057205A1

  公开（公告）日：2015-04-23

  The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

  本发明包括公式(I)的化合物。其中：R1、R2、R3、R4、R5、R6、R7、R8和R9在说明书中定义。本发明还包括治疗或改善综合症、障碍或疾病的方法，其中所述综合症、障碍或疾病为类风湿性关节炎或银屑病。本发明还包括通过管理一个治疗有效量的至少一个权利要求1的化合物来调节哺乳动物中的RORγt活性的方法。
• Homoleptic Zincate‐Promoted Room‐Temperature Halogen–Metal Exchange of Bromopyridines
  作者：Nguyet Trang Thanh Chau、Maxime Meyer、Shinsuke Komagawa、Floris Chevallier、Yves Fort、Masanobu Uchiyama、Florence Mongin、Philippe C. Gros

  DOI：10.1002/chem.201001664

  日期：2010.11.2

  Homoleptic lithium tri‐ and tetraalkyl zincates were reacted with a set of bromopyridines. Efficient and chemoselective bromine–metal exchanges were realized at room temperature with a substoichiometric amount of nBu4ZnLi2⋅TMEDA reagent (1/3 equiv; TMEDA=N,N,N′,N′‐tetramethylethylenediamine). This reactivity contrasted with that of tBu4ZnLi2⋅TMEDA, which was inefficient below one equivalent. DFT calculations

  均三酸锌和四烷基锌酸锂与一组溴吡啶反应。高效和化学选择性溴-金属交换是在室温下以低于化学计算量实现Ñ卜4 ZnLi 2 ⋅TMEDA试剂（1/3当量; TMEDA = Ñ，Ñ，N' ，N'四甲基乙二胺）。该反应性与t Bu 4 ZnLi 2的反应性相反⋅TMEDA，在一个当量以下效率低下。DFT计算使我们能够合理化反应中N⋅⋅⋅Li稳定的聚吡啶基锌盐的形成。使用化学计量的试剂也可以实现二溴吡啶的一锅双功能化。在溴吡啶中直接形成CZn键使我们能够进行有效的Negishi型交叉偶联。
• LTA4 Hydrolase inhibitors
  申请人：G.D. SEARLE & CO.

  公开号：EP1221441A2

  公开（公告）日：2002-07-10

  The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.

  本发明提供了具有公式Ar1-Q-Ar2-Y-R-Z的化合物及其药用可接受的盐，其中Ar1和Ar2是可选地取代的芳基部分，Z是可选地取代的含氮部分，可以是环状、环状或双环状的胺，或可选地取代的单环或双环的含氮杂芳基部分；Q是能够连接两个芳基团的连接基团；R是烷基亚基；Y是能够连接芳基团和烷基亚基的连接基团，并且其中Z通过氮原子与R键合。本发明的化合物和药物组合物在治疗由LTB4产生介导的炎症性疾病中是有用的，例如银屑病、溃疡性结肠炎、炎症性肠病和哮喘。
• The cooperative effect of Lewis pairs in the Friedel–Crafts hydroxyalkylation reaction: a simple and effective route for the synthesis of (±)-carbinoxamine
  作者：Adhikesavan Harikrishnan、Jayakumar Sanjeevi、Chinnasamy Ramaraj Ramanathan

  DOI：10.1039/c4ob02597k

  日期：——

  An efficient C–C bond formation strategy between aromatic/heteroaromatic π-nucleophiles and Lewis acid activated aldehydes is described. This aromatic electrophilic substitution reaction of arenes or heteroarenes is facilitated by Lewis acid AlBr3. Aromatic rings with electron donating substituents are excellent nucleophilic counterparts in this reaction, generating carbinols in excellent yields (61–94%)

  描述了芳族/杂芳族π-亲核试剂与路易斯酸活化醛之间有效的CC键形成策略。路易斯酸AlBr 3促进了芳烃或杂芳烃的芳族亲电取代反应。具有给电子取代基的芳香环在该反应中是极好的亲核对应物，可产生高收率的甲醇（61-94％）。在某些反应性醛和芳香族π-亲核试剂通过反应性碳正离子形成的情况下，也见证了三芳基甲烷的形成。三芳基甲烷的生成可通过以下方式更大程度地减少通过路易斯碱（例如吡啶）与烷氧基铝中间体配位的第二个π-亲核试剂加成的阻滞作用。在存在AlBr 3的情况下，各种脂肪醛也经历了Friedel-Crafts型羟烷基化反应，并以中等收率（41-53％）生成了预期的甲醇。该方案已成功地以单锅法成功用于治疗上重要的组胺H 1拮抗剂（±）-carbinoxamine的合成。