4-(adamantan-1-yloxy)-3-oxo-2-(triphenyl-λ⁵-phosphanylidene)butyric acid benzyl ester | 269071-39-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(adamantan-1-yloxy)-3-oxo-2-(triphenyl-λ⁵-phosphanylidene)butyric acid benzyl ester
• 英文别名: 4-(Adamantan-1-yloxy)-3-oxo-2-(triphenyl-l5-phosphanylidene)-butyric acid benzyl ester；Benzyl 4-(1-adamantyloxy)-3-oxo-2-(triphenyl-lambda5-phosphanylidene)butanoate；benzyl 4-(1-adamantyloxy)-3-oxo-2-(triphenyl-λ5-phosphanylidene)butanoate
• CAS: 269071-39-8
• 化学式: C₃₉H₃₉O₄P
• 分子量: 602.71
• InChiKey: HCITVLIMMPHMSM-UHFFFAOYSA-N

物化性质

• 沸点：
  722.5±70.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(adamantan-1-yloxy)-3-oxo-2-(triphenyl-λ⁵-phosphanylidene)butyric acid benzyl ester 在 palladium on activated charcoal Oxone 、 ammonium acetate 、 四丁基溴化铵 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 52.0h， 生成 5-(Adamantan-1-yloxymethyl)-2-(2,4,6-trimethyl-phenyl)-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  优化一系列新型的2,4,5-三取代的咪唑类作为有效的胆囊收缩素2（CCK2）拮抗剂的体外和体内特性。

  摘要：

  新型的2,4,5-三取代的咪唑基胆囊收缩素2（CCK（2））受体拮抗剂的结构的系统优化提供了具有纳摩尔受体亲和力的类似物。这些化合物的效价现在与基于双环杂芳族化合物5（JB93182）和6（JB95008）的效价相当，后者使用基于场点的分子建模方法设计了初始实例。通过抑制五肽胃泌素刺激的清醒犬的酸分泌可以判断，它们也具有口服活性，这与基于双环杂芳香族化合物的化合物（由于胆道消除而无效）相反。通过用醚氧置换特定的亚甲基来增加亲水性，如3-{[5-（金刚烷-1-基氧甲基）-2-环己基-1H-咪唑-4-羰基]氨基}苯甲酸中的苯甲酸（53）一样，对受体亲和力的影响很小，但显着提高了口服药的效力。 。比较血浆药代动力学和对十二指肠内推注53和6后五肽胃泌素刺激的酸输出的抑制作用，表明53吸收良好，半衰期更长，并且不受早期系列的消除途径的影响。

  DOI：

  10.1021/jm0490686
• 作为产物：
  描述：

  (adamantan-1-yloxy)-acetic acid 在 氯化亚砜 、 N,O-双三甲硅基乙酰胺 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 16.25h， 生成 4-(adamantan-1-yloxy)-3-oxo-2-(triphenyl-λ⁵-phosphanylidene)butyric acid benzyl ester
  参考文献：
  名称：

  优化一系列新型的2,4,5-三取代的咪唑类作为有效的胆囊收缩素2（CCK2）拮抗剂的体外和体内特性。

  摘要：

  新型的2,4,5-三取代的咪唑基胆囊收缩素2（CCK（2））受体拮抗剂的结构的系统优化提供了具有纳摩尔受体亲和力的类似物。这些化合物的效价现在与基于双环杂芳族化合物5（JB93182）和6（JB95008）的效价相当，后者使用基于场点的分子建模方法设计了初始实例。通过抑制五肽胃泌素刺激的清醒犬的酸分泌可以判断，它们也具有口服活性，这与基于双环杂芳香族化合物的化合物（由于胆道消除而无效）相反。通过用醚氧置换特定的亚甲基来增加亲水性，如3-{[5-（金刚烷-1-基氧甲基）-2-环己基-1H-咪唑-4-羰基]氨基}苯甲酸中的苯甲酸（53）一样，对受体亲和力的影响很小，但显着提高了口服药的效力。 。比较血浆药代动力学和对十二指肠内推注53和6后五肽胃泌素刺激的酸输出的抑制作用，表明53吸收良好，半衰期更长，并且不受早期系列的消除途径的影响。

  DOI：

  10.1021/jm0490686

文献信息

• Gastrin and cholecystokinin receptor ligands (III)
  申请人：——

  公开号：US20030191116A1

  公开（公告）日：2003-10-09

  Compounds of formula (I) and their pharmaceutically acceptable salts are ligands at gastrin and/or cholecystokinin receptors. X and Y are independently ═N—, —N(R 5 )—(R 5 being selected from H, Me, Et, Pr, Bn, OH and —CH 2 COOR 6 , wherein R 6 represents H, Me, Et, Pr or Bn), ═CH—, —O— or —S—; n is from 1 to 4; A is an optionally substituted 5- or 6-membered carbocyclic ring wherein (a) 1 or 2 C atoms may optionally be replaced by N, O and/or S atoms, (b) A is fused with the aromatic group in formula (I) to form a fused bicycle, and (c) the ring containing X and Y is linked to a C atom of A; R 1 is H or C 1 to C 15 hydrocarbyl wherein up to three C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; R 2 is selected from H, Me, Et, Pr and OH, each R 2 being independently selected from H, Me, Et, Pr and OH when n is greater than 1; R 3 (when n is 1) is selected from H, Me, Et and Pr; or (when n is greater than 1) each R 3 is independently selected from H, Me, Et and Pr, or two R 3 groups on neighbouring carbn atoms are linked to form a C 3 to C 6 carbocylic ring, or two R 3 groups are absent from neighbouring carbon atoms which are linked by a double bond; or R 2 and R 3 on the same carbon atom together represent an ═O group; R 4 is C 1 to C 15 hydrocarbyl wherein up to two C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; V is —CO—NH—SO 2 —Ph, —SO 2 —NH—CO—Ph, —CH 2 OH, or a group of the formula —R 7 U, (wherein U is —COOH, tetrazolyl, —CONHOH or —SO 3 H; and R 7 is a bond; C 1 to C 6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; —O—(C 1 to C 3 alkylene)—; —SO 2 NR 8 —CHR 9 —; —CO—NR 8 —CHR 9 —, R 8 and R 9 being independently selected from H and methyl; or —NH—(CO) c —CH 2 , c being 0 or 1); or a pharmaceutically acceptable salt thereof. Compositions comprising a compound a formula (I) are also described. 1

  公式（I）的化合物及其药学上可接受的盐是胃泌素和/或胆囊收缩素受体的配体。X和Y分别独立为═N—、—N(R5)—（R5选自H、Me、Et、Pr、Bn、OH和—CH2COOR6，其中R6代表H、Me、Et、Pr或Bn）、═CH—、—O—或—S—；n为1至4；A是一个可选择替代的5-或6-成员碳环，其中（a）1或2个C原子可选择替换为N、O和/或S原子，（b）A与公式（I）中的芳香基融合形成一个融合的双环，并且（c）含有X和Y的环与A的一个C原子连接；R1为H或C1至C15烃基，其中最多可有三个C原子可选择替换为N、O和/或S原子，最多可有三个H原子可选择替换为卤素原子；R2选自H、Me、Et、Pr和OH，当n大于1时，每个R2独立选择自H、Me、Et、Pr和OH；R3（当n为1时）选自H、Me、Et和Pr；或（当n大于1时）每个R3独立选择自H、Me、Et和Pr，或相邻碳原子上的两个R3基团连接形成一个C3到C6的碳环，或相邻碳原子上缺少两个R3基团，这两个基团由双键连接；或同一碳原子上的R2和R3共同表示一个═O基团；R4为C1至C15烃基，其中最多可有两个C原子可选择替换为N、O和/或S原子，最多可有三个H原子可选择替换为卤素原子；V为—CO—NH—SO2—Ph、—SO2—NH—CO—Ph、—CH2OH或式—R7U的基团（其中U为—COOH、四唑基、—CONHOH或—SO3H；而R7为键；C1至C6烃基亚烷，可选择地被羟基、氨基或乙酰胺基替代；—O—（C1至C3烷基）—；—SO2NR8—CHR9—；—CO—NR8—CHR9—，R8和R9独立选择自H和甲基；或—NH—（CO）c—CH2，c为0或1）；或其药学上可接受的盐。还描述了包含公式（I）化合物的组合物。
• Gastrin and cholecystokinin receptor ligands(II)
  申请人：——

  公开号：US20030199565A1

  公开（公告）日：2003-10-23

  Substituted imidazoles (1) are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure. Pharmaceutical compositions containing the novel imidazoles and pharmaceutical methods using them, alone and in conjunction with other drugs, especially diuretics and non-steroidal antiinflammatory drugs (NSAID's) are also described.

  取代咪唑（1）可作为血管紧张素II受体拮抗剂。这些化合物具有治疗高血压和充血性心力衰竭的活性。还描述了含有新型咪唑的药物组合物和使用它们的药物方法，单独或与其他药物一起使用，特别是利尿剂和非甾体抗炎药（NSAID）。
• US6878734B2
  申请人：——

  公开号：US6878734B2

  公开（公告）日：2005-04-12
• US7034048B2
  申请人：——

  公开号：US7034048B2

  公开（公告）日：2006-04-25
• [EN] GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS (III)<br/>[FR] LIGANDS (III) DES RECEPTEURS DE LA CHOLECYSTOKININE ET DE LA GASTRINE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2001085724A1

  公开（公告）日：2001-11-15

  Compounds of formula (I) and their pharmaceutically acceptable salts are ligands at gastrin and/or cholecystokinin receptors. X and Y are independently =N-, -N(R5)-(R5 being selected from H, Me, Et, Pr, Bn, OH and -CH¿2COOR?6, wherein R6 represents H, Me, Et, Pr or Bn), =CH-, -O- or -S-; n is from 1 to 4; A is an optionally substituted 5- or 6- membered carbocyclic ring wherein (a) 1 or 2 C atoms may optionally be replaced by N, O and/or S atoms, (b) A is fused with the aromatic group in formula (I) to form a fused bicycle, and (c) the ring containing X and Y is linked to a C atom of A; R1 is H or C¿1? to C15 hydrocarbyl wherein up to three C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; R?2¿ is selected from H, Me, Et, Pr and OH, each R2 being independently selected from H, Me, Et, Pr and OH when n is greater than 1; R3 (when n is 1) is selected from H, Me, Et and Pr; or (when n is greater than 1) each R3 is independently selected from H, Me, Et and Pr, or two R3 groups on neighbouring carbn atoms are linked to form a C¿3? to C6 carbocylic ring, or two R?3¿ groups are absent from neighbouring carbon atoms which are linked by a double bond; or R?2 and R3¿ on the same carbon atom together represent an =O group; R4 is C1 to C15 hydrocarbyl wherein up to two C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; V is -CO-NH-SO2-Ph, -SO2-NH-CO-Ph, -CH2OH, or a group of the formula -R7U, (wherein U is -COOH, tetrazolyl, -CONHOH or -SO¿3?H; and R?7¿ is a bond; C¿1? to C6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; -O-(C1 to C3 alkylene)-; -SO2NR?8-CHR9¿-; -CO-NR?8-CHR9-, R8 and R9¿ being independently selected from H and methyl; or -NH-(CO)¿c?-CH2, c being 0 or 1); or a pharmaceutically acceptable salt thereof. Compositions comprising a compound a formula (I) are also described.