4-(4-hydroxyphenyl)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrobenzopyran | 57897-46-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 4-(4-hydroxyphenyl)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrobenzopyran
• 英文别名: trans-2,2-dimethyl-3-phenyl-4-(p-hydroxyphenyl)-7-methoxychroman；trans-2,2-Dimethyl-3-phenyl-4-(p-hydroxyphenyl)-7-methoxy chroman；4-[(3R,4R)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrochromen-4-yl]phenol
• CAS: 57897-46-8
• 化学式: C₂₄H₂₄O₃
• 分子量: 360.453
• InChiKey: PHKFTVVFCJTISE-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxyphenyl)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrobenzopyran 在 potassium carbonate 、 一水合肼 作用下， 以 丙酮 为溶剂， 反应 11.0h， 生成 2-[4-(l(-)-trans-3,4-dihydro-2,2-dimethyl-3-phenyl-7-methoxybenzopyran-4-yl)phenoxy]propionic acid hydrazide
  参考文献：
  名称：

  Effect of side-chain alteration on hormonal activity of nonsteroidal estrogen antagonists

  摘要：

  Incorporation of novel side-chains in 3,4-diaryl chromans, an established nucleus present in the nonsteroidal estrogen antagonist centchroman, has been carried out. The effect of variation in the nature of the chain on relative binding affinity (RBA) to estrogen receptor, estrogenicity, and antiestrogenicity has been studied. Presence of hydrazide residue on cis- and trans-3,4-diaryl chromans led to relatively higher RBA and estrogenicity as compared with corresponding acids and esters.

  DOI：

  10.1007/s00044-009-9238-0
• 作为产物：
  描述：

  cis-2,2-Dimethyl-3-phenyl-4-(p-hydroxyphenyl)-7-methoxychroman 在 镍 正丁基锂 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 正己烷 、 二甲基亚砜 、 丙酮 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 59.0h， 生成 4-(4-hydroxyphenyl)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrobenzopyran
  参考文献：
  名称：

  Antifertility agents. 38. Effect of the side chain and its position on the activity of 3,4-diarylchromans

  摘要：

  In a study of the effect of the substituent on the receptor binding affinity (RBA), estrogenicity, and antiimplantation (AI) activity in trans-3,4-diarylchromans, it has been found that demethylation of trans-2, 2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychroman (centchroman, 1) to the corresponding 7-hydroxy compound (7) results in a 20-fold increase in RBA (112%) without any appreciable change in AI activity. On the other hand, absence of the pyrrolidinoethyl group from the 4-phenyl residue (6) leads to a drop in both RBA and AI activity. A chain length of two to three carbon atoms and a pyrrolidino ring appear to be necessary for activity in these compounds. It has been found that while the trans isomers with the tertiary aminoalkoxy side chain in the para position of the 4-phenyl radical were the most active, in the corresponding cis-chromans and chromenes, analogues with this chain in the meta position were most active; the ortho substituted compounds of all these series were inactive. In 3-phenyl-substituted compounds, the trans isomer carrying the p-hydroxy substituent (33) was found to be the most active; the corresponding pyrrolidinoethyl ether (13) showed a lower order of activity. The implication of these observations on the mapping of the different subsites on the receptor has been discussed.

  DOI：

  10.1021/jm00358a026

文献信息

• Differentiation of skeletal osteogenic progenitor cells to osteoblasts with 3,4-diarylbenzopyran based amide derivatives: Novel osteogenic agents
  作者：Atul Gupta、Imran Ahmad、Jyoti Kureel、Aijaz A. John、Eram Sultan、Debabrata Chanda、Naresh Kumar Agarwal、Alauddin、Wahajuddin、S. Prabhaker、Amita Verma、Divya Singh

  DOI：10.1016/j.ejmech.2016.05.023

  日期：2016.10

  A series of 3,4-diarylbenzopyran based amide derivatives was synthesized and evaluated for osteogenic activity in in vitro and in vivo models of osteoporosis. Compounds 17a, 21b–c and 22a–b showed significant osteogenic activity in osteoblast differentiation assay. Among the synthesized compounds, 22b was identified as lead molecule which showed significant osteogenic activity at 1 pM concentration

  合成了一系列基于3,4-二芳基苯并吡喃的酰胺衍生物，并在骨质疏松症的体外和体内模型中评估了其成骨活性。化合物17a，21b–c和22a–b在成骨细胞分化试验中显示出显着的成骨活性。在合成的化合物中，鉴定出的铅分子22b在成骨细胞分化试验中浓度为1 pM时和在雌激素缺乏的balb / c小鼠模型中剂量为1 mg kg -1体重时显示出显着的成骨活性。体外骨矿化和成骨标记基因的表达vizBMP-2，RUNX-2，OCN和1型胶原蛋白进一步证实了22b的成骨潜力。小鼠颅骨成骨细胞（MCOs）中雌激素受体α和β（ER-α和ER-β）的基因表达研究表明，可能22b通过优先激活雌激素受体β发挥成骨功效。22b的体内药代动力学，雌激素性和急性毒性研究表明，它具有良好的生物利用度，分别在1 mg kg -1的剂量和高达1000 mg kg -1体重的剂量时没有子宫雌激素性。
• [EN] (3R, 4R)-TRANS-3,4-DIARYLCHROMAN DERIVATIVES WITH ESTROGENIC ACTIVITY<br/>[FR] DERIVES DE (3R, 4R)-TRANS-3,4-DIARYLCHROMANE A ACTIVITE OESTROGENIQUE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2005035517A1

  公开（公告）日：2005-04-21

  The present invention relates to compounds of the formula I in which substituents R<2> and R<3> are arranged in trans-configuration, Formula (I), wherein: R<1> is H or C1-C6 alkyl; C3-C7 cycloalkyl; R<2> is phenyl, optionally substituted with 1 to 5 substituents independently selected from the group comprising OH, C1-C6 -alkyl, halogen, nitro, cyano, SH, SR<4>, trihalo-C1-C6-alkyl, C1-C6 -alkoxy and phenyl, wherein R<4> is C1-C6 alkyl;R<3> is phenyl substituted with OR<5> wherein R<5> has the Formula (II), (III) or (IV) , wherein Y is chosen from NHR<4>, NR<4>2, NHCOR<4>, NHSO2R<4>, CONHR<4>, CONR<4>, CONR<4>2, COOH, COOR<4>, SO2R<4>, SOR<4>, SONHR<4>, SONR<4>2, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group comprising H, OH, halogen, nitro, cyano, SH, SR<4>, trihalo-C1-C6- alkyl, C1-C6-alkyl and C1-C6 -alkoxy, preferably NHR<4>, NR2<4>, or a nitrogen heterocycle, wherein R<4> is as defined above, and the esters, ethers, and salts of the compounds of formula I, optionally along pharmaceutically acceptable excipients, a process for the preparation of the same, and a method of preventing and/or treating estrogen-related disease conditions in a subject using compounds of formula (I), or its salts, optionally along with pharmaceutically acceptable excipients.

  本发明涉及具有以下结构的化合物I，其中取代基R2和R3以反式配置排列，式（I）中：R1为H或C1-C6烷基；C3-C7环烷基；R2为苯基，可选地取代为从OH、C1-C6-烷基、卤素、硝基、氰基、SH、SR4、三卤代C1-C6-烷基、C1-C6-烷氧基和苯基中独立选择的1至5个取代基，其中R4为C1-C6烷基；R3为取代为OR5的苯基，其中R5具有式（II）、（III）或（IV），其中Y选择自NHR4、NR42、NHCOR4、NHSO2R4、CONHR4、CONR4、CONR42、COOH、COOR4、SO2R4、SOR4、SONHR4、SONR42、一个饱和或不饱和的含有1至2个异原子（O、S和N）的杂环C3-C7环，可选地取代为从H、OH、卤素、硝基、氰基、SH、SR4、三卤代C1-C6-烷基、C1-C6-烷基和C1-C6-烷氧基中独立选择的1至3个取代基，优选为NHR4、NR24，或氮杂环，其中R4如上定义，以及式I化合物的酯、醚和盐，可选地与药学上可接受的赋形剂一起使用，一种制备该化合物的方法，以及使用式（I）的化合物或其盐，可选地与药学上可接受的赋形剂一起，预防和/或治疗受试者的雌激素相关疾病病况的方法。
• (3R, 4R)-trans-3, 4-diarylchroman derivatives and a method for the prevention and/or treatment of estrogen dependent diseases
  申请人：Sangita

  公开号：US20050070597A1

  公开（公告）日：2005-03-31

  The present invention relates to compounds of the formula I in which substituents R 2 and R 3 are arranged in trans-configuration: wherein: R 1 is H or C1-C6 alkyl; C3-C7 cycloalkyl; R 2 is phenyl, optionally substituted with 1 to 5 substituents independently selected from the group comprising OH, C1-C6-alkyl, halogen, nitro, cyano, SH, SR 4, trihalo-C1-C6-alkyl, C1-C6-alkoxy and phenyl, wherein R 4 is C1-C6 alkyl; R 3 is phenyl substituted with OR 5 wherein R 5 has the formula (II), (III) or (IV) wherein Y is chosen from NHR 4 , NR 4 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , CONR 4 , CONR 4 2 , COOH, COOR 4 , SO 2 R 4 , SOR 4 , SONHR 4 , SONR 4 2, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group comprising H, OH, halogen, nitro, cyano, SH, SR 4 , trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy, preferably NHR 4 , NR 2 4 , or a nitrogen heterocycle, wherein R 4 is as defined above, and the esters, ethers, and salts of the compounds of formula I, optionally along pharmaceutically acceptable excipients, a process for the preparation of the same, and a method of preventing and/or treating estrogen-related disease conditions in a subject using compounds of formula 1, or its salts, optionally along with pharmaceutically acceptable excipients.

  本发明涉及公式I的化合物，其中取代基R2和R3以反式结构排列：其中：R1为H或C1-C6烷基；C3-C7环烷基；R2为苯基，可选地取代为1至5个取代基，独立选择自包括OH，C1-C6-烷基，卤素，硝基，氰基，SH，SR4，三卤代-C1-C6-烷基，C1-C6-烷氧基和苯基的群；其中R4为C1-C6烷基；R3为取代为OR5的苯基，其中R5具有公式（II），（III）或（IV）其中Y从NHR4，NR42，NHCOR4，NHSO2R4，CONHR4，CONR4，CONR42，COOH，COOR4，SO2R4，SOR4，SONHR4，SONR42，C3-C7杂环环，饱和或不饱和，含有一个或两个异原子，独立选择自O，S和N的群，可选地取代为1至3个取代基，独立选择自H，OH，卤素，硝基，氰基，SH，SR4，三卤代-C1-C6-烷基，C1-C6-烷基和C1-C6-烷氧基，优选为NHR4，NR24，或氮杂环，其中R4如上定义，以及公式I化合物的酯，醚和盐，可选地与药学上可接受的赋形剂一起使用，一种制备相同的方法，以及使用公式1的化合物或其盐，可选地与药学上可接受的赋形剂一起，预防和/或治疗受体内的雌激素相关疾病症状的方法。
• Synthesis and cytotoxic activity of benzopyran-based platinum(II) complexes
  作者：Atul Gupta、Sanat K. Mandal、Valérie Leblanc、Caroline Descôteaux、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.bmcl.2008.06.013

  日期：2008.7

  A series of benzopyran-based platinum complexes of types 4 and 5 were synthesized as potential anticancer agents. The novel compounds were synthesized in several steps using simple and efficient chemistry. The newly synthesized compounds were evaluated for their biological efficacy and showed significant in vitro cytotoxic activity in different hormone-dependent and -independent breast cancer cell lines. Docking and other molecular modeling experiments were also performed for one of the potent compounds, 5f, which showed that both the possible enantiomeric forms (5f with 3R, 4R and 5f with 3S, 4S) of the molecule have comparable lowest energy (for 5f with 3R, 4R, -31.953 kcal/mol and for 5f with 3S, 4S, -31.944 kcal/mol). The 3D QSAR was examined for the derivatives of both enantiomeric forms and a novel relationship for the 3S, 4S derivatives is discussed. (c) 2008 Elsevier Ltd. All rights reserved.
• Sharma, Indra; Ray, Suprabhat; Ansari, A. H., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 516 - 519
  作者：Sharma, Indra、Ray, Suprabhat、Ansari, A. H.

  DOI：——

  日期：——