3-(3-氨基苯基)丙酸叔丁酯 | 269071-88-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(3-氨基苯基)丙酸叔丁酯
• 英文名称: (3-amino-phenyl)-propionic acid tert-butyl ester
• 英文别名: Tert-butyl 3-(3-aminophenyl)propanoate
• CAS: 269071-88-7
• 化学式: C₁₃H₁₉NO₂
• mdl: MFCD23972938
• 分子量: 221.299
• InChiKey: PAXUMWVHPFOIIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-氨基苯基)丙酸叔丁酯 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-(3-(2-(5-cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-acetylamino)-phenyl)-propionic acid
  参考文献：
  名称：

  Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion

  摘要：

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.

  DOI：

  10.1021/jm070139l
• 作为产物：
  描述：

  tert-butyl 3-nitrocinnamic acid 在 palladium on activated charcoal 氢气 作用下， 以 1,4-二氧六环 为溶剂， 以100%的产率得到3-(3-氨基苯基)丙酸叔丁酯
  参考文献：
  名称：

  Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion

  摘要：

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.

  DOI：

  10.1021/jm070139l

文献信息

• Optimization of the in Vitro and in Vivo Properties of a Novel Series of 2,4,5-Trisubstituted Imidazoles as Potent Cholecystokinin-2 (CCK₂) Antagonists
  作者：Ildiko M. Buck、James W. Black、Tracey Cooke、David J. Dunstone、John D. Gaffen、Eric P. Griffin、Elaine A. Harper、Robert A. D. Hull、S. Barret Kalindjian、Elliot J. Lilley、Ian D. Linney、Caroline M. R. Low、Iain M. McDonald、Michael J. Pether、Sonia P. Roberts、Nigel P. Shankley、Mark E. Shaxted、Katherine I. M. Steel、David A. Sykes、Matthew J. Tozer、Gillian F. Watt、Martin K. Walker、Laurence Wright、Paul T. Wright

  DOI：10.1021/jm0490686

  日期：2005.11.1

  The systematic optimization of the structure of a novel 2,4,5-trisubstituted imidazole-based cholecystokinin-2 (CCK(2)) receptor antagonist afforded analogues with nanomolar receptor affinity. These compounds were now comparable in their potency to the bicyclic heteroaromatic-based compounds 5 (JB93182) and 6 (JB95008), from which the initial examples were designed using a field-point based molecular

  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。
• 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）。
• OXO-HETEROCYCLIC SUBSTITUTED CARBOXYLIC ACID DERIVATIVES AND THE USE THEREOF
  申请人：Hahn Michael

  公开号：US20110034450A1

  公开（公告）日：2011-02-10

  The present application relates to novel carboxylic acid derivatives having an oxo-substituted azaheterocyclic partial structure, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

  本申请涉及具有氧代取代的氮杂杂环部分结构的新型羧酸衍生物，其制备方法，其用于治疗和/或预防疾病的用途，以及其用于生产用于治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防心血管疾病的用途。
• [EN] BENZOTRIAZEPINE DERIVATIVES AND THEIR USE AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZOTRIAZEPINE ET LEUR UTILISATION EN TANT QUE LIGANDS DE RECEPTEUR DE LA GASTRINE ET DE LA CHOLECYSTOKININE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2004098610A1

  公开（公告）日：2004-11-18

  This invention relates to a compound of formula (I). The compound is useful for the treatment of gastrin related disorders.

  这项发明涉及一种化合物，其化学式为（I）。该化合物可用于治疗与胃泌素相关的疾病。
• [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）。