5-(Adamantan-1-yloxymethyl)-2-cyclohexyl-1H-imidazole-4-carboxylic Acid | 269071-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(Adamantan-1-yloxymethyl)-2-cyclohexyl-1H-imidazole-4-carboxylic Acid
• 英文别名: 5-(1-adamantyloxymethyl)-2-cyclohexyl-1H-imidazole-4-carboxylic acid
• CAS: 269071-42-3
• 化学式: C₂₁H₃₀N₂O₃
• 分子量: 358.481
• InChiKey: NATIBONRJKIETM-UHFFFAOYSA-N

物化性质

• 沸点：
  590.7±35.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(Adamantan-1-yloxymethyl)-2-cyclohexyl-1H-imidazole-4-carboxylic Acid 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-({[5-(Adamantan-1-yloxymethyl)-2-cyclohexyl-1H-imidazole-4-carbonyl]-hydrazono}-amino-methyl)-benzoic acid benzyl ester
  参考文献：
  名称：

  Gastrin and cholecystokinin receptor ligands(II)

  摘要：

  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）。

  公开号：

  US20030199565A1
• 作为产物：
  描述：

  (adamantan-1-yloxy)-acetic acid 在 palladium on activated charcoal Oxone 、 氯化亚砜 、 N,O-双三甲硅基乙酰胺 、 ammonium acetate 、 四丁基溴化铵 、 氢气 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 70.25h， 生成 5-(Adamantan-1-yloxymethyl)-2-cyclohexyl-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

文献信息

• Pharmaceutical compositions comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands
  申请人：——

  公开号：US20030195240A1

  公开（公告）日：2003-10-16

  Pharmaceutical compositions comprising a proton pump inhibitor and a compound of the formula (I) or its pharmaceutically acceptable salts, are useful in treating gastrointestinal disorders. 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—, S— or —O—; n is from 1 to 4; 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 carbon atoms which are linked by a double bond; or R 2 and R 3 on the same carbon atom 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 two H atoms may optionally be replaced by halogen atoms; Z is —(NR 7 ) a —CO—(NR 8 ) b — (wherein a is 0 or 1, b is 0 or 1, and R 7 and R 8 are independently selected from the groups recited above for R 6 ), —CO—NR 7 —CH 2 —CO—NR 8 —, —CO—O—, —CH 2 —CH 2 —, —CH═CH—, —CH 2 —NR— or a bond; Q is —R 9 V, or (II) (wherein R 9 is —CH 2 —; —CH 2 —CH 2 —; or (III) R 9 and R 8 , together with the nitrogen atom to which R 8 is attached, form a piperidine or pyrrolidine ring which is substitued by V; V is —CO—NH—SO 2 -Ph, SO 2 —NH—CO-Ph, —CH 2 OH, or a group of the formula —R 10 U, (wherein U is —COOH, tetrazolyl, —CONHOH— or —SO 3 H; and R 10 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 11 —CHR 12 —; —CO—NR 11 —CHR 12 —, R 11 and R 12 being independently selected from H and methyl; or —NH—(CO), —CH 2 —, c being 0 or 1); T is C 1 to C 6 hydrocarbyl, —NR 6 R 7 (wherein R 6 and R 7 are as defined above), —OMe, —OH, —CH 2 OH, halogen or trihalomethyl; m is 1 or 2; p is from 0 to 3; and q is from 0 to 2, with the proviso that q is 1 or 2 when Z is a bond). 1

  含有质子泵抑制剂和公式（I）或其药学上可接受的盐的化合物的制剂，对治疗胃肠道疾病有用。其中，X和Y分别是═N—，—N（R5）—（其中R5选择自H，Me，Et，Pr，Bn，—OH和— COOR6，其中R6代表H，Me，Et，Pr或Bn），═CH—，S—或—O—；n为1至4；R1为H或C1至C15的烃基，其中最多可有三个C原子被N，O和/或S原子取代，最多可有三个H原子被卤素原子取代；当n大于1时，R2选择自H，Me，Et，Pr和OH，每个R2独立选择自H，Me，Et，Pr和OH；当n为1时，R3选择自H，Me，Et和Pr；当n大于1时，每个R3独立选择自H，Me，Et和Pr，或被双键连接的相邻碳原子上的两个R3基团；或R2和R3在同一碳原子上连接形成C3到C6的环状碳基；或相邻碳原子上缺少两个R3基团，它们被双键连接；或R2和R3在同一碳原子上共同表示═O基团；R4为C1至C15的烃基，其中最多可有两个C原子被N，O和/或S原子取代，最多可有两个H原子被卤素原子取代；Z为—（NR7）a—CO—（NR8）b—（其中a为0或1，b为0或1，且R7和R8与上述R6中的基团独立选择），—CO—NR7—CH2—CO—NR8—，—CO—O—，— — —，—CH═CH—，— —NR—或键；Q为—R9V，或（II）（其中R9为— —；— — —；或（III）R9和R8与R8连接的氮原子一起形成被V取代的哌啶或吡咯烷环；V为—CO—NH—SO2-Ph，SO2—NH—CO-Ph，— OH或公式—R10U的基团（其中U为—COOH，四唑基，—CONHOH—或—SO3H；R10为键；C1至C6的烃基，可选地被羟基，氨基或乙酰胺基取代；—O—（C1至C3的烷基）-；—SO2NR11—CHR12—；—CO—NR11—CHR12—，其中R11和R12独立选择自H和甲基；或—NH—（CO），— —，其中c为0或1）；T为C1至C6的烃基，—NR6R7（其中R6和R7如上所定义），—OMe，—OH，— OH，卤素或三卤甲基；m为1或2；p为0至3；q为0至2，但当Z为键时，q为1或2。
• GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS
  申请人：JAMES BLACK FOUNDATION LIMITED

  公开号：EP1178969B1

  公开（公告）日：2005-07-13
• US6479531B1
  申请人：——

  公开号：US6479531B1

  公开（公告）日：2002-11-12
• US6878734B2
  申请人：——

  公开号：US6878734B2

  公开（公告）日：2005-04-12
• [EN] GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS (II)<br/>[FR] LIGANDS (II) DE RECEPTEUR DE LA GASTRINE ET DE LA CHOLECYSTOKININE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2001085723A1

  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-, -S-, or -O-; R1 is H or C¿1?-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 carbon atoms are linked to form a C¿3? to C6 carbocyclic 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 H or C¿1?-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; Z is a diradical derived from an optionally substituted aromatic or non-aromatic C5 or C6 carbocycle, wherein 1, 2 or 3 C atoms are optionally replaced by N, O and/or S; Q is a 6-membered aromatic carbocycle (optionally substituted with 1 or 2 V groups and/or 1, 2 or 3 T groups) wherein 1, 2 or 3 C atoms are optionally replaced by N; V is -CO-NH-SO2-Ph, -SO2-NH-CO-Ph, -CH2OH, 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 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); T is C1 to C6 hydrocarbyl, -NR?10R11¿ (wherein R?10 and R11¿ are independently selected from H, Me, Et, Pr or Bn), -OMe, -OH, -CH¿2?OH, halogen or trihalomethyl. Compositions comprising a compound of formula (I) are also described.