3-chloro-5-tert-butyl-2,6-dihydroxyacetophenone | 120034-10-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chloro-5-tert-butyl-2,6-dihydroxyacetophenone
• 英文别名: 1-(3-Tert-butyl-5-chloro-2,6-dihydroxyphenyl)ethanone
• CAS: 120034-10-8
• 化学式: C₁₂H₁₅ClO₃
• 分子量: 242.702
• InChiKey: IJFRFHKOZNBVFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-5-tert-butyl-2,6-dihydroxyacetophenone 在 sodium cyanoborohydride 、 zinc(II) iodide 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 4-hydroxy-7-chloro-5-tert-butyl-2-<(4'-methoxyphenyl)methyl>-3-methylbenzofuran
  参考文献：
  名称：

  Synthesis and structure-activity relationships of a novel class of 5-lipoxygenase inhibitors. 2-(Phenylmethyl)-4-hydroxy-3,5-dialkylbenzofurans: the development of L-656,224

  摘要：

  The synthesis of a series of 2-(phenylmethyl)-4-hydroxy-3,5-dialkylbenzofurans and their inhibitory effects against leukotriene biosynthesis and 5-lipoxygenase activity in vitro are described. Many compounds in this series were found to be potent inhibitors of LTB4 production by human polymorphonuclear leukocytes with IC50 values ranging from 7 to 100 nM. Structure-activity relationships of the series are presented. Within this series, 2-[(4'-methoxyphenyl)methyl]-4-hydroxy-3-methyl-5-propyl-7-chlorobenz ofuran (L-656,224) showed extremely potent activity, inhibiting leukotriene biosynthesis in intact human leukocytes (IC50 = 11 nM), as well as the 5-lipoxygenase reaction catalyzed by cell-free preparations from rat leukocytes (IC50 = 36 nM), human leukocytes (IC50 = 0.4 microM), and the purified enzyme from porcine leukocytes (IC50 = 0.4 microM). The compound also shows oral activity in a number of animal models in vivo.

  DOI：

  10.1021/jm00126a008

文献信息

• Benzofuran derivatives
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0338782A1

  公开（公告）日：1989-10-25

  Benzofuran derivatives are useful as inhibitors of mammalian leuktoriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation. The compounds are also useful as analgesics and as cytoprotective agents, and for these uses are made into pharmaceutical compositions. The compounds of the invention have the formula wherein: each R1 is independently hydrogen or C1 to C6 alkyl; R2 is hydrogen, C1 to C8 alkyl, -(CH2)n-het-Y, -(CH2)n-Q or - CH- Q, CH3 where Q is R3 is hydroxyl, , OCOCH2CH2COOH, OSO3H, or OPO3H2; each R4 is independently C1 to C6 alkyl; each R5 is independently H, C1 to C6 alkyl, or both R5s join to form a 5- or 6-membered ring with the N to which they are attached; Het is a heterocyclic group selected from pyridine, pyrazine, pyrimidine, oxazole, pyrazole, oxadiazole, tetrazole, quinoline, thiophene, furan, pyrrole, thiazole, thiadiazole, or imidazole; X is 0, S, SO, SO2; Y, Y1, Y2, Y3, Y4 and Z are each independently H, halogen, OH. C1 to C6 alkyl, C2 to C6 alkenyl, C1-6hydroxyalkyl, -COOR1, -COR1, nitro, carboxy (C1-6alkyl), C1 to C6 alkoxy, C1 to C6 alkylthio, -CH2SR1, OCH2CO2R1, and each n is independently 0 to 10; with the provisos that: (a) not all of R1, R2, Y, Y1, Y2, Y3, Y4, and Z are simultaneously H; (b) when up to 2 of R1, R2, Y, Y1, and Z are C1 to C2 alkyl, and the others of R1, R2, Y, Y1, and Z are H, then R3 is not OH; and (c) when n in is O and one of R3, Y, Y1 or Z is OH, then Ri is not H or Ci to C2 alkyl; or are acid-addition salts thereof.

  苯并呋喃衍生物可作为哺乳动物白细胞介素生物合成的抑制剂。因此，这些化合物是治疗过敏症、哮喘、心血管疾病和炎症的有效药物。这些化合物还可用作镇痛剂和细胞保护剂，并可用于制成药物组合物。本发明的化合物具有如下式子 其中 每个 R1 独立地为氢或 C1 至 C6 烷基； R2 是氢、C1 至 C8 烷基、-(CH2)n-het-Y、-(CH2)n-Q 或-CH- Q, CH3 其中 Q 是 R3 是羟基、 OCOCH2CH2COOH、OSO3H 或 OPO3H2；每个 R4 独立地是 C1 至 C6 烷基； 每个 R5 独立地为 H、C1-C6 烷基，或两个 R5 与所连接的 N 连接形成 5 或 6 元环； Het 是杂环基团，选自吡啶、吡嗪、嘧啶、噁唑、吡唑、噁二唑、四唑、喹啉、噻吩、呋喃、吡咯、噻唑、噻二唑或咪唑； X 是 0、S、SO、SO2； Y、Y1、Y2、Y3、Y4 和 Z 各自独立地是 H、卤素、OH C1-C6烷基、C2-C6烯基、C1-6羟基烷基、-COOR1、-COR1、硝基、羧基（C1-6烷基）、C1-C6烷氧基、C1-C6烷硫基、-CH2SR1、OCH2CO2R1、 且每个 n 独立地为 0 至 10；但有以下条件： (a) 并非所有 R1、R2、Y、Y1、Y2、Y3、Y4 和 Z 同时都是 H； (b) 当 R1、R2、Y、Y1 和 Z 中最多有 2 个是 C1 至 C2 烷基，而 R1、R2、Y、Y1 和 Z 中的其它是 H 时，则 R3 不是 OH；以及 (c) 当 n 为 O 且 R3、Y、Y1 或 Z 中的一个为 OH 时，则 Ri 不是 H 或 Ci 至 C2 烷基；或为其酸加成盐。
• LAU, CHEUK K.;BELANGER, PATRICE C.;SCHEIGETZ, JOHN;DUFRESNE, CLAUDE;WILLI+, J. MED. CHEM., 32,(1989) N, C. 1190-1197
  作者：LAU, CHEUK K.、BELANGER, PATRICE C.、SCHEIGETZ, JOHN、DUFRESNE, CLAUDE、WILLI+

  DOI：——

  日期：——
• BELANGER, PATRICE C.;SCHEIGETZ, JOHN;ROKACH, JOSHUA
  作者：BELANGER, PATRICE C.、SCHEIGETZ, JOHN、ROKACH, JOSHUA

  DOI：——

  日期：——
• US4863958A
  申请人：——

  公开号：US4863958A

  公开（公告）日：1989-09-05
• US5087638A
  申请人：——

  公开号：US5087638A

  公开（公告）日：1992-02-11