1-hydroxy-2-(3-decyloxyphenyl)ethylidene-1,1-bisphosphonic acid | 1059677-34-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: 1-hydroxy-2-(3-decyloxyphenyl)ethylidene-1,1-bisphosphonic acid
• 英文别名: BPH-754；{2-[3-(Decyloxy)phenyl]-1-hydroxy-1-phosphonoethyl}phosphonic acid；[2-(3-decoxyphenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid
• CAS: 1059677-34-7
• 化学式: C₁₈H₃₂O₈P₂
• 分子量: 438.395
• InChiKey: MHLLAPRPDYGFFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 三(三甲代甲硅烷基)亚磷酸盐 、 甲醇 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 1-hydroxy-2-(3-decyloxyphenyl)ethylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Inhibition of Geranylgeranyl Diphosphate Synthase by Bisphosphonates: A Crystallographic and Computational Investigation

  摘要：

  We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg2+ that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 angstrom. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents.

  DOI：

  10.1021/jm800325y

文献信息

• Bisphosphonate Compounds and Methods with Enhanced Potency for Multiple Targets including FPPS, GGPPS, AND DPPS
  申请人：OLDFIELD Eric

  公开号：US20080255070A1

  公开（公告）日：2008-10-16

  The disclosure provides, inter alia, novel bisphosphonate compounds and methods of making and using such compounds. In certain embodiments, compounds of the invention include bisphosphonates that are capable of selectively inhibiting one or more of farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS), and decaprenyl pyrophosphate synthase (DPPS). In preferred embodiments, compounds of the invention are capable of selectively inhibiting two or more of FPPS, GGPPS, and DPPS. In embodiments, compounds and methods of the invention demonstrate superior activity levels, such as in the anti-cancer context, immunostimulation context, and other contexts, which in several cases exceed the activity levels of previous generation bisphosphonate drugs by orders of magnitude. In embodiments, the invention provides compounds and methods in connection with research and therapeutic applications, e.g., for tumor or cancer cell growth inhibition, activation of gammadelta T cells, inhibition of certain enzymes related to the mevalonate metabolic pathway, bone resorption diseases, cancer, immune disorders, immunotherapy, and infectious diseases.
• US8012949B2
  申请人：——

  公开号：US8012949B2

  公开（公告）日：2011-09-06
• [EN] BISPHOSPHONATE COMPOUNDS AND METHODS WITH ENHANCED POTENCY FOR MULTIPLE TARGETS INCLUDING FPPS, GGPPS, AND DPPS<br/>[FR] COMPOSÉS BISPHOSPHONATES ET PROCÉDÉS PRÉSENTANT UN POTENTIEL AMÉLIORÉ POUR CIBLES MULTIPLES INCLUANT FPPS, GGPPS, ET DPPS
  申请人：UNIV ILLINOIS

  公开号：WO2008128056A1

  公开（公告）日：2008-10-23

  [EN] The disclosure provides, inter alia, novel bisphosphonate compounds and methods of making and using such compounds. In certain embodiments, compounds of the invention include bisphosphonates that are capable of selectively inhibiting one or more of farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS), and decaprenyl pyrophosphate synthase (DPPS). In preferred embodiments, compounds of the invention are capable of selectively inhibiting two or more of FPPS, GGPPS, and DPPS. In embodiments, compounds and methods of the invention demonstrate superior activity levels, such as in the anti-cancer context, immunostimulation context, and other contexts, which in several cases exceed the activity levels of previous generation bisphosphonate drugs by orders of magnitude. In embodiments, the invention provides compounds and methods in connection with research and therapeutic applications, e.g., for tumor or cancer cell growth inhibition, activation of gammadelta T cells, inhibition of certain enzymes related to the mevalonate metabolic pathway, bone resorption diseases, cancer, immune disorders, immunotherapy, and infectious diseases.
  [FR] La présente invention concerne notamment de nouveaux composés bisphosphonates et des procédés de réalisation et d'utilisation de ces composés. Dans certains modes de réalisation, les composés de la présente invention incluent des bisphosphonates qui sont capables d'inhiber sélectivement un ou plusieurs des éléments suivants : synthase diphosphate farnésyle (FPPS), géranylgéranyle synthase diphosphate (GGPPS), et décaprényle synthase pyrophosphate (DPPS). Dans des modes de réalisation préférés, les composés de l'invention sont capables d'inhiber sélectivement deux éléments ou plus parmi FPPS, GGPPS et DPPS. Dans certains modes de réalisation, les composés et les procédés de l'invention présentent des niveaux d'activité supérieurs, par exemple dans le contexte anticancéreux, le contexte d'immunostimulation et d'autres contextes ; dans plusieurs cas, ces niveaux dépassent les niveaux d'activité des médicaments bisphosphonates de génération antérieure en ordre de grandeur. Dans certains modes de réalisation, la présente invention porte sur des composés et des procédés liés à la recherche et aux applications thérapeutiques, par exemple pour l'inhibition de la croissance tumorale ou de la croissance des cellules cancéreuses, l'activation de cellules T gammadelta, l'inhibition de certaines enzymes liées à la voie métabolique du mévalonate, les maladies de résorption osseuse, le cancer, les troubles immuns, l'immunothérapie, et les maladies infectieuses.