4-(4-氟苯基)-5-吡啶-4-基-1,3-恶唑 | 166895-06-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(4-氟苯基)-5-吡啶-4-基-1,3-恶唑
• 英文名称: 4-[4-(4-fluoro-phenyl)-oxazol-5-yl]-pyridine
• 英文别名: 4-(4-Fluorophenyl)-5-(pyridin-4-yl)oxazole；4-(4-Fluorophenyl)-5-(4-pyridyl)oxazole；4-[4-(4-Fluorophenyl)-1,3-oxazol-5-yl]pyridine；4-(4-fluorophenyl)-5-pyridin-4-yl-1,3-oxazole
• CAS: 166895-06-3
• 化学式: C₁₄H₉FN₂O
• 分子量: 240.237
• InChiKey: NKWYMYOCYVDEFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-氟苯基)-5-吡啶-4-基-1,3-恶唑 在 bis(1,5-cyclooctadiene)nickel (0) 、 copper(l) iodide 、 1,2-双(二苯基膦基)苯 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 2-Ethynyl-4-(4-fluorophenyl)-5-pyridin-4-yl-1,3-oxazole
  参考文献：
  名称：

  Syntheses and structure–activity relationships for some triazolyl p38α MAPK inhibitors

  摘要：

  The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38 alpha MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38 alpha MAPK inhibitor 88 (IC50 = 0.096 mu M) displayed the most promising in vitro activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.034
• 作为产物：
  描述：

  1-(4-氟苯基)-2-(4-吡啶基)乙酮 在 硫酸 、 溴 、 溶剂黄146 作用下， 反应 0.25h， 生成 4-(4-氟苯基)-5-吡啶-4-基-1,3-恶唑
  参考文献：
  名称：

  Syntheses and structure–activity relationships for some triazolyl p38α MAPK inhibitors

  摘要：

  The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38 alpha MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38 alpha MAPK inhibitor 88 (IC50 = 0.096 mu M) displayed the most promising in vitro activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.034

文献信息

• Oxazoles for treating cytokine mediated diseases
  申请人：SmithKline Beecham Corporation

  公开号：US06288062B1

  公开（公告）日：2001-09-11

  This invention relates to the novel oxazole compounds of Formula (I) and novel pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of inhibiting cytokines and the treatment of cytokine mediated diseases, in mammals, thereby by administration of an effective amount of a compound according to Formula (I).

  这项发明涉及到式（I）的新型噁唑化合物以及包括式（I）化合物和药用可接受的稀释剂或载体的新型药物组合物。该发明还涉及一种通过给哺乳动物按照式（I）的化合物的有效量进行给药来抑制细胞因子和治疗细胞因子介导疾病的方法。
• Heteroaryl-cyclic acetals
  申请人：Collis Alan

  公开号：US20050090501A1

  公开（公告）日：2005-04-28

  Compounds of formula (I) are described in which Het is a five or six membered heteroaromatic ring of the formula in which one of R 1 and R 2 is optionally substituted heteroaryl and the other is optionally substituted heteroaryl or optionally substituted aryl; X 1 is a bond, X 3 and X 4 are each independently N or C and X 2 and X 5 are independently CH, N, NH, O or S; or X 3 and X 4 are C, one of X 1 , X 2 and X 5 is N and the others are N or CH; but excluding compounds in which X 1 is a bond, one of X 2 and X 5 is N and the other is NH and X 3 and X 4 are both C; R 3 represents a group -L 1 -R 6 ; R 4 represents hydrogen, alkyl or hydroxyalkyl; or R 3 and R 4 , when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C═CH 2 ; R 5 represents hydrogen or alkyl; and m is zero or an integer 1 or 2; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates of compounds of formula (I) and N-oxides thereof, and their prodrugs. The compounds are TNF inhibitors and are useful as pharmaceuticals.

  描述了式(I)化合物，其中Het是式的五元或六元杂环芳香环：其中R1和R2中的一个是可选取代的杂芳基，另一个是可选取代的杂芳基或可选取代的芳基；X1是键，X3和X4分别独立地是N或C，X2和X5独立地是CH、N、NH、O或S；或者X3和X4是C，X1、X2和X5中的一个是N，其他是N或CH；但不包括其中X1是键，X2和X5中的一个是N，另一个是NH，X3和X4都是C的化合物；R3表示一个-L1-R6基团；R4表示氢、烷基或羟基烷基；或者当附加到同一个碳原子时，R3和R4可以与所述碳原子形成环状烷基、环状烯基或杂环烷基环或C═CH2基团；R5表示氢或烷基；m为零或整数1或2；以及其N-氧化物和其前药；化合物的式(I)和其N-氧化物的药学上可接受的盐和溶剂；这些化合物是TNF抑制剂，可用于制药。
• Pyridyl-oxazoles and their use as cytokines inhibitors
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1306377A2

  公开（公告）日：2003-05-02

  This invention relates to the novel oxazole compounds of Formula (I) and novel pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of inhibiting cytokines and the treatment of cytokine mediated diseases, in mammals, thereby by administration of an effective amount of a compound according to Formula (I).

  本发明涉及式(I)的新型噁唑化合物和由式(I)化合物和药学上可接受的稀释剂或载体组成的新型药物组合物。 本发明还涉及一种抑制细胞因子和治疗细胞因子介导的疾病的方法，该方法通过在哺乳动物体内施用有效量的根据式（I）的化合物来实现。
• HETEROARYL-CYCLIC ACETALS
  申请人：Aventis Pharma Limited

  公开号：EP1140916B1

  公开（公告）日：2002-11-13
• SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors
  作者：Laszlo Revesz、Franco E Di Padova、Thomas Buhl、Roland Feifel、Hermann Gram、Peter Hiestand、Ute Manning、Alfred G Zimmerlin

  DOI：10.1016/s0960-894x(00)00200-6

  日期：2000.6

  The 4-hydroxypiyeridine substituent was found to confer high p38 selectivity devoid of COX-1 affinity, when attached to a series of pyridinyl substituted heterocycles. Pyridinyloxazole 11 showed a promising in vivo profile with bioavailability of 64% and ED50 in rat collagen induced arthritis of 10 mg/kg po bid. In contrast to pyridinylimidazoles such as SE 203580, 11 did not inhibit human cytochrome P450 isoenzymes. (C) 2000 Elsevier Science Ltd. All rights reserved.