2-adamantan-1-ylmethyl-5-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester | 269070-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-adamantan-1-ylmethyl-5-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-(1-adamantylmethyl)-5-phenyl-1H-pyrrole-3-carboxylate
• CAS: 269070-78-2
• 化学式: C₂₄H₂₉NO₂
• 分子量: 363.5
• InChiKey: BGEFYKPSJWCYCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-adamantan-1-ylmethyl-5-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以94%的产率得到2-adamantan-1-ylmethyl-5-phenyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Pharmaceutical compositions comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands

  摘要：

  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—CH2COOR6，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—，—CH2—CH2—，—CH═CH—，—CH2—NR—或键；Q为—R9V，或（II）（其中R9为—CH2—；—CH2—CH2—；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，—CH2OH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），—CH2—，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，—CH2OH，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。

  公开号：

  US20030195240A1
• 作为产物：
  描述：

  4-adamantan-1-yl-3-oxobutyric acid ethyl ester 在 ammonium acetate 、 potassium carbonate 、 溶剂黄146 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 60.0h， 生成 2-adamantan-1-ylmethyl-5-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Scaffold Hopping with Molecular Field Points:  Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

  摘要：

  A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK2) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK1. In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.

  DOI：

  10.1021/jm049069y

文献信息

• Gastrin and cholecystokinin receptor ligands
  申请人：James Black Foundation Limited

  公开号：US06479531B1

  公开（公告）日：2002-11-12

  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)—═CH—, —S— or —O—. n is from 1 to 4; R1 is H or C1 to C15 hydrocarbyl R2 is selected from H, Me, Et, Pr and OH, R3 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 C3 to C6 carbocylic ring, or R2 and R3 on the same carbon atom together represent an ═O group; R4 is C1 to C15 hydrocarbyl Z is —(NR7)a—CO—(NR8)b— (wherein a is 0 or 1, b is 0 or 1, —CO—NR7—CH2—CO—NR8—, —CO—O—, —CH2—CH2—, —CH═CH—, —CH2—NR8— or a bond; Q is —R9V, or (II), (wherein R9 is —CH2—; —CH2—CH2—; or (III), R9 and R8, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substituted by V; V is —CO—NH—SO2—Ph, —SO2—NH—CO—Ph, —CH2OH, or a group of the formula —R10U, (wherein U is —COOH, tetrazolyl, —CONHOH— or —SO3H; and R10 is a bond; C1 to C6 hydrocarbylene, —O—(C1 to C3 alkylene)—; —SO2NR11—CHR12—; —CO—NR11—CHR12—, or —NH—(CO)c—CH2—, c being 0 or 1).

  化合物的结构式（I）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独立地为═N—，—N(R5)—═CH—，—S—或—O—。n为1至4；R1为H或C1至C15烃基；R2从H，Me，Et，Pr和OH中选择；R3从H，Me，Et和Pr中选择；或（当n大于1时）每个R3独立地从H，Me，Et和Pr中选择，或相邻碳原子上的两个R3基团连接形成C3至C6碳环，或R2和R3在同一碳原子上共同表示一个═O基团；R4为C1至C15烃基；Z为—(NR7)a—CO—(NR8)b—（其中a为0或1，b为0或1，—CO—NR7—CH2—CO—NR8—，—CO—O—，—CH2—CH2—，—CH═CH—，—CH2—NR8—或键；Q为—R9V，或（II），（其中R9为—CH2—；—CH2—CH2—；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，—CH2OH，或具有式—R10U的基团，（其中U为—COOH，四唑基，—CONHOH—或—SO3H；R10为键；C1至C6烃基亚烷，—O—（C1至C3亚烷基）—；—SO2NR11—CHR12—；—CO—NR11—CHR12—，或—NH—（CO）c—CH2—，其中c为0或1）。
• 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—CH2COOR6，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—，—CH2—CH2—，—CH═CH—，—CH2—NR—或键；Q为—R9V，或（II）（其中R9为—CH2—；—CH2—CH2—；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，—CH2OH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），—CH2—，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，—CH2OH，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。
• [EN] GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] LIGANDS DES RECEPTEURS DE LA GASTRINE ET DE LA CHOLECYSTOKININE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2000027823A1

  公开（公告）日：2000-05-18

  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)- =CH-, -S- or -O-. n is from 1 to 4; R1 is H or C¿1? to C15 hydrocarbyl R?2¿ is selected from H, Me, Et, Pr and OH, R¿3? 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 R3 groups on neighbouring carbon atoms are linked to form a C¿3? to C6 carbocylic ring, or R?2 and R3¿ on the same carbon atom together represent an =O group; R4 is C1 to C15 hydrocarbyl Z is -(NR7)a-CO-(NR8)b- (wherein a is 0 or 1, b is 0 or 1, -CO-NR7-CH2-CO-NR8-, -CO-O-, -CH¿2?-CH2-, -CH=CH-, -CH2-NR?8¿- or a bond; Q is -R9V, or (II), (wherein R9 is -CH¿2?-; -CH2-CH2-; or (III), R?9 and R8¿, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substituted by V; V is -CO-NH-SO¿2?-Ph, -SO2-NH-CO-Ph, -CH2OH, 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 C6 hydrocarbylene, -O-(C1 to C3 alkylene)-; -SO2NR?11-CHR12¿-; -CO-NR?11-CHR12¿-, or -NH-(CO)¿c?-CH2-, c being 0 or 1).

  式(I)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独立地为=N-，-N（R5）-，=CH-，-S-或-O-。n为1至4；R1为H或C1至C15的烃基；R2从H，Me，Et，Pr和OH中选择，R3从H，Me，Et和Pr中选择；或（当n大于1时）每个R3独立地从H，Me，Et和Pr中选择，或相邻碳原子上的两个R3基团连接形成C3至C6的环烷基，或R2和R3在同一碳原子上共同表示一个=O基团；R4为C1至C15的烃基，Z为-(NR7)a-CO-(NR8)b-（其中a为0或1，b为0或1，-CO-NR7-CH2-CO-NR8-，-CO-O-，-CH2-CH2-，-CH=CH-，-CH2-NR8-或键；Q为-R9V，或（II），（其中R9为-CH2-；-CH2-CH2-；或（III），R9和R8，连同R8所连接的氮原子，形成被V取代的哌嗪或吡咯烷环；V为-CO-NH-SO2-Ph，-SO2-NH-CO-Ph，-CH2OH，或式-R10U的基团（其中U为-COOH，四唑基，-CONHOH-或-SO3H；R10为键；C1至C6的烃亚基，-O-（C1至C3的烷基）-；-SO2NR11-CHR12-；-CO-NR11-CHR12-，或-NH-（CO）c-CH2-，其中c为0或1）。
• GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS
  申请人：JAMES BLACK FOUNDATION LIMITED

  公开号：EP1178969A1

  公开（公告）日：2002-02-13
• US6479531B1
  申请人：——

  公开号：US6479531B1

  公开（公告）日：2002-11-12