1-(4-methylsulfanylphenyl)-3-phenylprop-2-yn-1-ol | 742699-16-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(4-methylsulfanylphenyl)-3-phenylprop-2-yn-1-ol
• 英文别名: 1-(4-(methylthio)phenyl)-3-phenylprop-2-yn-1-ol
• CAS: 742699-16-7
• 化学式: C₁₆H₁₄OS
• 分子量: 254.353
• InChiKey: XZBOBYWYKQNWBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-methylsulfanylphenyl)-3-phenylprop-2-yn-1-ol 在 manganese(IV) oxide 、 sodium hydride 作用下， 以 二甲基亚砜 、 丙酮 为溶剂， 反应 1.0h， 生成 6-(4-methylsulfanylphenyl)-3,4-diphenylpyran-2-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship Studies of 3,4,6-Triphenylpyran-2-ones as Selective Cyclooxygenase-2 Inhibitors

  摘要：

  A group of regioisomeric 3,4,6-triphenylpyran-2-ones with a MeSO2 pharmacophore at the paraposition of either a C-3 phenyl or a C-4 phenyl substituent on the central six-membered pyran-2-one ring were prepared and evaluated in vitro for their abilities to inhibit the isozymes COX-1 and COX-2. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position of the C-6 phenyl ring attached to the central pyranone, showed that 6-(4-methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was the most potent and selective COX-2 inhibitor (COX-2 IC50 = 0.02 muM; COX-1 IC50 > 100 muM) with a high COX-2 selectivity index (SI > 5000) relative to the reference drugs celecoxib (COX-2 IC50 = 0.07 muM; SI = 474) and rofecoxib (COX-2 IC50 = 0.50 muM; SI > 200). 6-(4-Methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was a more potent oral antiinflammatory agent (ID50 = 5.6 mg/kg) than celecoxib (ID50 = 10.8 mg/kg) in a carrageenan-induced rat paw edema assay. In a 4% NaCl-induced abdominal constriction assay, a 5 mg/kg oral dose of 12e exhibited good analgesic activity at different time intervals producing 37.5 and 69% inhibition of writhing at 30 and 60 min, respectively. In contrast, the corresponding 6-(4-methoxyphenyl)-4-(4-methanesulfonylphenyl)-3-phenylpyran-2-one regiosiomer (12o) was a less potent and selective COX-2 inhibitor (COX-2 IC50 = 0.45 muM; SI = 70). A molecular modeling study for 12e indicated that the p-OMe substituent on the C-6 phenyl ring interacts with the COX-2 binding site amino acids Ile(345), Val(349), Leu(359), Leu(531), and Met(535) and that the OMe substituent may be responsible for proper orientation of the C-3 p-SO2Me-phenyl ring within the COX-2 secondary pocket (Gln(192), Arg(513), and Phe(518)). These results show that the COX-2 selectivity and potency of 3,4,6-triphenylpyranone regioisomers can be modulated by appropriate placement of the p-SO2Me pharmacophore on either the C-3 or C-4 phenyl moiety. In addition, electronic properties at the para-position of a C-6 phenyl substituent on the central pyranone ring govern COX-2 inhibitory potency and selectivity by controlling the orientation of the p-SO2Me pharmacophore within the COX-2 secondary pocket.

  DOI：

  10.1021/jm049939b
• 作为产物：
  描述：

  苯乙炔 、 4-(甲基巯基)苯甲醛 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 1-(4-methylsulfanylphenyl)-3-phenylprop-2-yn-1-ol
  参考文献：
  名称：

  用于构建苯并[f]异吲哚二聚体的区域和非对映选择性自由基二聚反应

  摘要：

  本研究提出了一种合成苯并[ f ]异吲哚二聚体的新方法，涉及级联环化和氧化自由基二聚化。我们的方法允许在单个反应中形成多达五个碳-碳键，表现出显着的非对映选择性和区域选择性。通过实验和计算相结合的方式研究了其机理和区域选择性。

  DOI：

  10.1021/acs.orglett.4c00587

文献信息

• Copper-Catalyzed Direct Coupling of Unprotected Propargylic Alcohols with P(O)H Compounds: Access to Allenylphosphoryl Compounds under Ligand- and Base-Free Conditions
  作者：Gaobo Hu、Changkai Shan、Weizhu Chen、Pengxiang Xu、Yuxing Gao、Yufen Zhao

  DOI：10.1021/acs.orglett.6b03028

  日期：2016.12.2

  The first facile and efficient copper-catalyzed direct C–P cross-coupling of unprotected propargylic alcohols with P(O)H compounds has been developed, providing a general, one-step approach to construct valuable allenylphosphoryl frameworks with operational simplicity and high step- and atom-economy under ligand-, base-, and additive-free conditions.

  已经开发出了第一个简便而有效的铜催化的未保护的炔丙醇与P（O）H化合物的直接C–P交叉偶联方法，它提供了一种通用的一步法来构建有价值的烯丙基磷酰基骨架，且操作简便且操作步骤高。和无配体，无碱和无添加剂条件下的原子经济。
• Enantioselective Alkynylation of Aromatic Aldehydes Catalyzed by a Sterically Highly Demanding Chiral-at-Rhodium Lewis Acid
  作者：Shipeng Luo、Xiao Zhang、Yu Zheng、Klaus Harms、Lilu Zhang、Eric Meggers

  DOI：10.1021/acs.joc.7b01394

  日期：2017.9.1

  The enantioselective catalytic alkynylation of aromatic aldehydes is reported using a sterically highly hindered bis-cyclometalated rhodium-based Lewis acid catalyst featuring the octahedral metal as the only stereogenic center. Yields of 58–98% with 79–98% enantiomeric excess were achieved using 1–2 mol % of catalyst. This work complements previous work from our laboratory on the enantioselective alkynylation

  据报道，使用空间高度受阻的双环金属化铑基路易斯酸催化剂，以八面体金属为唯一立体异构中心，可以对芳族醛进行对映选择性催化炔基化反应。使用1-2 mol％的催化剂可实现58-98％的收率和79-98％的对映体过量。这项工作的补充我们实验室上的2-三氟乙酰基咪唑对映选择性炔基化以前的工作（化学- 。J.欧洲药典 2016，22，11977-11981）和三氟甲基酮（J.化学会志。 2017，139，4322 –4325）使用具有八面体金属中心手性的催化剂。
• 10.1021/acs.joc.4c00977
  作者：Zhang, Zhi、Ji, Miao-Miao、Wu, Xiao-Feng、He, Yong-Yu、Peng, Jin-Bao

  DOI：10.1021/acs.joc.4c00977

  日期：——

  group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The

  2,3-联烯酰胺是一类重要的不饱和基团取代的羰基化合物。已开发出一种钯催化的乙酸炔丙酯与胺的氨基羰基化反应，用于合成三/四取代的 2,3-丙二烯酰胺。由乙酸炔丙酯制备了多种三/四取代的 2,3-丙二烯酰胺，收率良好至优异。该反应反应条件温和，官能团耐受性良好。几种天然产物和药物的后期修饰进一步凸显了该方法的适用性。
• Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1 (COX-1) inhibitors
  作者：Xue-Ping Chu、Qing-Fa Zhou、Shen Zhao、Fei-Fei Ge、Mian Fu、Jia-Peng Chen、Tao Lu

  DOI：10.1016/j.cclet.2013.01.005

  日期：2013.2

  A group of 3-amino-2-pyrones were synthesized and their biological activities were evaluated for inhibiting cyclooxygenase (COX) activity. This study has led to the identification of COX-1-selective inhibitors. Among the tested compounds, the compound 5j exhibited the most potent COX-1 inhibitory activity (IC50 = 19.32 mu g/mL) and COX-1 selectivity index (SI = 41.98). (C) 2013 Qing-Fa Zhou. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Design, Synthesis, and Structure−Activity Relationship Studies of 3,4,6-Triphenylpyran-2-ones as Selective Cyclooxygenase-2 Inhibitors
  作者：P. N. Praveen Rao、Md. Jashim Uddin、Edward E. Knaus

  DOI：10.1021/jm049939b

  日期：2004.7.1

  A group of regioisomeric 3,4,6-triphenylpyran-2-ones with a MeSO2 pharmacophore at the paraposition of either a C-3 phenyl or a C-4 phenyl substituent on the central six-membered pyran-2-one ring were prepared and evaluated in vitro for their abilities to inhibit the isozymes COX-1 and COX-2. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position of the C-6 phenyl ring attached to the central pyranone, showed that 6-(4-methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was the most potent and selective COX-2 inhibitor (COX-2 IC50 = 0.02 muM; COX-1 IC50 > 100 muM) with a high COX-2 selectivity index (SI > 5000) relative to the reference drugs celecoxib (COX-2 IC50 = 0.07 muM; SI = 474) and rofecoxib (COX-2 IC50 = 0.50 muM; SI > 200). 6-(4-Methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was a more potent oral antiinflammatory agent (ID50 = 5.6 mg/kg) than celecoxib (ID50 = 10.8 mg/kg) in a carrageenan-induced rat paw edema assay. In a 4% NaCl-induced abdominal constriction assay, a 5 mg/kg oral dose of 12e exhibited good analgesic activity at different time intervals producing 37.5 and 69% inhibition of writhing at 30 and 60 min, respectively. In contrast, the corresponding 6-(4-methoxyphenyl)-4-(4-methanesulfonylphenyl)-3-phenylpyran-2-one regiosiomer (12o) was a less potent and selective COX-2 inhibitor (COX-2 IC50 = 0.45 muM; SI = 70). A molecular modeling study for 12e indicated that the p-OMe substituent on the C-6 phenyl ring interacts with the COX-2 binding site amino acids Ile(345), Val(349), Leu(359), Leu(531), and Met(535) and that the OMe substituent may be responsible for proper orientation of the C-3 p-SO2Me-phenyl ring within the COX-2 secondary pocket (Gln(192), Arg(513), and Phe(518)). These results show that the COX-2 selectivity and potency of 3,4,6-triphenylpyranone regioisomers can be modulated by appropriate placement of the p-SO2Me pharmacophore on either the C-3 or C-4 phenyl moiety. In addition, electronic properties at the para-position of a C-6 phenyl substituent on the central pyranone ring govern COX-2 inhibitory potency and selectivity by controlling the orientation of the p-SO2Me pharmacophore within the COX-2 secondary pocket.