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4-cycloheptyl-2,3-dioxobutyric acid ethyl ester | 269070-85-1

中文名称
——
中文别名
——
英文名称
4-cycloheptyl-2,3-dioxobutyric acid ethyl ester
英文别名
Ethyl 4-cycloheptyl-2,3-dioxobutanoate
4-cycloheptyl-2,3-dioxobutyric acid ethyl ester化学式
CAS
269070-85-1
化学式
C13H20O4
mdl
——
分子量
240.299
InChiKey
BFMPNXJJMJOXJH-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    3.5
  • 重原子数:
    17
  • 可旋转键数:
    6
  • 环数:
    1.0
  • sp3杂化的碳原子比例:
    0.77
  • 拓扑面积:
    60.4
  • 氢给体数:
    0
  • 氢受体数:
    4

反应信息

  • 作为反应物:
    描述:
    4-cycloheptyl-2,3-dioxobutyric acid ethyl ester 在 palladium on activated charcoal 4-二甲氨基吡啶sodium hydroxide 、 ammonium acetate 、 氢气1-羟基苯并三唑溶剂黄1461-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下, 以 四氢呋喃甲醇乙醇N,N-二甲基甲酰胺 为溶剂, 反应 50.0h, 生成 3-[(5-Cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carbonyl)-amino]-benzoic acid
    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
  • 作为产物:
    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
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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—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)。
  • [EN] PHARMACEUTICAL COMPOSITIONS COMPRISING PROTON PUMP INHIBITORS AND GASTRIN/CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES COMPRENANT DES INHIBITEURS DE LA POMPE A PROTONS ET DES LIGANDS DU RECEPTEUR DES GASTRINES/CHOLECYSTOKININES
    申请人:BLACK JAMES FOUNDATION
    公开号:WO2001085167A1
    公开(公告)日:2001-11-15
    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(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-; n is from 1 to 4; 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 carbon atoms which are linked by a double bond; or R?2 and R3¿ on the same carbon atom are linked to form a C¿3? to C6 carbocylic ring, or two R3 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 two H atoms may optionally be replaced by halogen atoms; Z is -(NR7)a-CO-(NR8)b- (wherein a is 0 or 1, b is 0 or 1, and R?7 and R8¿ are independently selected from the groups recited above for R6), -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 substitued 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, optionally substituted by hydroxy, amino or acetamido; -O-(C1 to C3 alkylene)-; -SO2NR?11-CHR12¿-;-CO-NR?11 -CHR12-, R11 and R12¿ being independently selected from H and methyl; or -NH-(CO)¿c?-CH2-, c being 0 or 1); T is C1 to C6 hydrocarbyl, -NR?6R7¿ (wherein R?6 and R7¿ 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).
    含有质子泵抑制剂和公式(I)化合物或其药学上可接受的盐的制剂,可用于治疗胃肠道疾病。其中,X和Y独立地等于=N-,-N(R5)-(其中R5选择自H,Me,Et,Pr,Bn,-OH和-CH2COOR6,其中R6表示H,Me,Et,Pr或Bn),=CH-,-S-或-O-;n为1至4;R1为H或C1至C15烃基,其中最多可以用N,O和/或S原子替换最多三个C原子,并且最多可以用卤素原子替换最多三个H原子;当n大于1时,R2从H,Me,Et,Pr和OH中选择,每个R2独立地从H,Me,Et,Pr和OH中选择;当n为1时,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,或者相邻碳原子上的两个R3基团通过双键连接;或R2和R3在同一碳原子上连接形成C3至C6的环状碳基环,或相邻碳原子上缺少两个R3基团,这些碳原子由双键连接;或R2和R3在同一碳原子上一起表示=O基团;R4为C1至C15烃基,其中最多可以用N,O和/或S原子替换最多两个C原子,并且最多可以用卤素原子替换最多两个H原子;Z为-(NR7)a-CO-(NR8)b-(其中a为0或1,b为0或1,且R7和R8独立地从上述R6群中选择),-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,形成一个被V取代的哌啶或吡咯烷环;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烃基亚烷基,可选择性地被羟基,氨基或乙酰氨基取代;-O-(C1至C3烷基)-;-SO2NR11-CHR12-,-CO-NR11-CHR12-,其中R11和R12独立地选择自H和甲基;或-NH-(CO)c-CH2-,其中c为0或1);T为C1至C6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,但前提是当Z为键时,q为1或2。
  • GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS
    申请人:JAMES BLACK FOUNDATION LIMITED
    公开号: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
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马来酰基乙酸 顺-3-己烯-1-丙酮酸 青霉酸 钠氟草酰乙酸二乙酯 醚化物 酮霉素 辛酸,2,4-二羰基-,乙基酯 草酸乙酯钠盐 草酰乙酸二乙酯钠盐 草酰乙酸二乙酯 草酰乙酸 草酰丙酸二乙酯 苯乙酰丙二酸二乙酯 苯丁酸,b-羰基-,2-丙烯基酯 聚氧化乙烯 羟基-(3-羟基-2,3-二氧代丙基)-氧代鏻 磷酸二氢2-{(E)-2-[4-(二乙胺基)-2-甲基苯基]乙烯基}-1,3,3-三甲基-3H-吲哚正离子 碘化镝 硬脂酰乙酸乙酯 甲氧基乙酸乙酯 甲氧基乙酰乙酸酯 甲基氧代琥珀酸二甲盐 甲基4-环己基-3-氧代丁酸酯 甲基4-氯-3-氧代戊酸酯 甲基4-氧代癸酸酯 甲基4-氧代月桂酸酯 甲基4-(甲氧基-甲基磷酰)-2,2,4-三甲基-3-氧代戊酸酯 甲基3-羰基-2-丙酰戊酸酯 甲基3-氧代十五烷酸酯 甲基2-氟-3-氧戊酯 甲基2-氟-3-氧代己酸酯 甲基2-氟-3-氧代丁酸酯 甲基2-乙酰基环丙烷羧酸酯 甲基2-乙酰基-4-甲基-4-戊烯酸酯 甲基2-乙酰基-2-丙-2-烯基戊-4-烯酸酯 甲基2,5-二氟-3-氧代戊酸酯 甲基2,4-二氟-3-氧代戊酸酯 甲基2,4-二氟-3-氧代丁酸酯 甲基1-异丁酰基环戊烷羧酸酯 甲基1-乙酰基环戊烷羧酸酯 甲基1-乙酰基环丙烷羧酸酯 甲基(2Z,4E,6E)-2-乙酰基-7-(二甲基氨基)-2,4,6-庚三烯酸酯 甲基(2S)-2-甲基-4-氧代戊酸酯 甲基(1R,2R)-2-乙酰基环丙烷羧酸酯 瑞舒伐他汀杂质 瑞舒伐他汀杂质 环氧乙烷基甲基乙酰乙酸酯 环戊戊烯酸,Β-氧代,乙酯 环戊基(氧代)乙酸乙酯 环戊[b]吡咯-6-腈,八氢-2-氧-,[3aS-(3aalpha,6alpha,6aalpha)]-(9CI)