methyl 3-(6-cyanopyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate | 1025482-52-3

• 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: methyl 3-(6-cyanopyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate
• CAS: 1025482-52-3
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: WGFBKYYZMQPGHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  63
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(6-cyanopyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate 在 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 methyl 3-(6-(formamidomethyl)pyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate
  参考文献：
  名称：

  Heterocyclic glucocorticoid receptor modulators with a 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core

  摘要：

  A series of heterocyclic glucocorticoid receptor (GR) modulators with 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl) propanamide core are described. Structure-activity relationships suggest a combination of H-bond acceptor and a 4-fluorophenyl moiety as being important structural components contributing to the glucocorticoid receptor binding and functional activity for this series of GR modulators. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.049
• 作为产物：
  描述：

  acetic acid (6-chloro-pyridin-3-yl)-phenyl-methyl ester 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 四氯化钛 、 锌 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 生成 methyl 3-(6-cyanopyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate
  参考文献：
  名称：

  Heterocyclic glucocorticoid receptor modulators with a 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core

  摘要：

  A series of heterocyclic glucocorticoid receptor (GR) modulators with 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl) propanamide core are described. Structure-activity relationships suggest a combination of H-bond acceptor and a 4-fluorophenyl moiety as being important structural components contributing to the glucocorticoid receptor binding and functional activity for this series of GR modulators. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.049

文献信息

• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Dhar T. G. Murali

  公开号：US20100190820A1

  公开（公告）日：2010-07-29

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, and/or AP-1 and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I): its enantiomers, diastereomers, or a pharmaceutically-acceptable salt, or hydrate, thereof, wherein the group X is O or (R x )(R y ); is heterocyclo or heteroaryl; E is —N—, —NR 1 —, —O—, —C(═O), —S—, —SO 2 —, or —CR 2 —; F is —N—, —NR 1a , —O—, —C(═O), —S—, —SO 2 —, or —CR 2a —; G is independently N, —NR 1b —, —O—, —C(═O), —S—, —SO 2 — or —CR 2b — provided that the heterocyclic ring formed does not contain a S—S or S—O bond and at least one of E, F and G is a hetero atom; and Ma, R x , R y , R 1 , R 1a , R 1b , R 2 , R 2a , R 2b , R 4 , R 5a , R 6 , R 7 , X, Z a and Z are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases employing said compounds.

  提供了一种新型的非甾体化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括炎症和免疫性疾病、肥胖和糖尿病，其结构如下式（I）：其对映体、非对映体或药用可接受的盐或水合物，其中基团X为O或（Rx）（Ry）；异环或杂环芳基；E为—N—、—NR1—、—O—、—C(═O)、—S—、—SO2—或—CR2—；F为—N—、—NR1a—、—O—、—C(═O)、—S—、—SO2—或—CR2a—；G独立地为N、—NR1b—、—O—、—C(═O)、—S—、—SO2—或—CR2b—，但所形成的杂环环不含有S—S或S—O键，且E、F和G中至少有一个是杂原子；以及Ma、Rx、Ry、R1、R1a、R1b、R2、R2a、R2b、R4、R5a、R6、R7、X、Za和Z的定义如本文所述。还提供了药物组合物和治疗炎症或免疫相关疾病的方法，采用上述化合物。
• Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US07994190B2

  公开（公告）日：2011-08-09

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, and/or AP-1 and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I):, its enantiomers, diastereomers, or a pharmaceutically-acceptable salt, or hydrate, thereof, wherein the group X is O or (Rx)(Ry); is heterocyclo or heteroaryl; E is —N—, —NR1—, —O—, —C(═O), —S—, —SO2—, or —CR2—; F is —N—, —NR1a, —O—, —C(═O), —S—, —SO2—, or —CR2a—; G is independently N, —NR1b—, —O—, —C(═O), —S—, —SO2— or —CR2b— provided that the heterocyclic ring formed does not contain a S—S or S—O bond and at least one of E, F and G is a hetero atom; and Ma, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, R4, R5a, R6, R7, X, Za and Z are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases employing said compounds.

  提供了一种新型非甾体化合物，其结构公式为(I)：及其对映异构体、顺式异构体或其药学上可接受的盐或水合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括炎症和免疫性疾病、肥胖和糖尿病，其中，X基团为O或(Rx)(Ry);为杂环或杂环芳基; E为—N—、—NR1—、—O—、—C(═O)、—S—、—SO2—或—CR2—; F为—N—、—NR1a—、—O—、—C(═O)、—S—、—SO2—或—CR2a—; G独立地为N、—NR1b—、—O—、—C(═O)、—S—、—SO2—或—CR2b—，前提是所形成的杂环不含S—S或S—O键，且E、F和G中至少有一个为杂原子; Ma、Rx、Ry、R1、R1a、R1b、R2、R2a、R2b、R4、R5a、R6、R7、X、Za和Z的定义如本文所述。还提供了含有该化合物的药物组合物和治疗炎症或免疫相关疾病的方法。
• HETEROCYCLIC COMPOUNDS AS MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KAPPA-B ACTIVITY
  申请人：Bristol-Myers Squibb Company

  公开号：EP2089389A2

  公开（公告）日：2009-08-19
• US7994190B2
  申请人：——

  公开号：US7994190B2

  公开（公告）日：2011-08-09
• [EN] MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF<br/>[FR] MODULATEUR DU RÉCEPTEUR DE GLUCOCORTICOÏDES, AP-1, ET/OU ACTIVITÉ DE NF-KB ET LEUR UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2008057855A2

  公开（公告）日：2008-05-15

  (EN) Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, and/or AP-1 and/or NF-ϰB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I):, its enantiomers, diastereomers, or a pharmaceutically-acceptable salt, or hydrate, thereof, wherein the group X is O or (Rx)(Ry); is heterocyclo or heteroaryl; E is -N-, -NR1-, -O-, -C(=O), -S-, -SO2-, or -CR2-; F is -N-, -NR1a, -O-, -C(=O), -S-, -SO2-, or -CR2a-; G is independently N, -NR1b-, -O-, -C(=O), -S-, -SO2- or -CR2b- provided that the heterocyclic ring formed does not contain a S-S or S-O bond and at least one of E, F and G is a hetero atom; and Ma, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, R4, R5a, R6, R7, X, Za and Z are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases employing said compounds.(FR) L'invention concerne de nouveaux composés non stéroïdaux qui sont utiles dans le traitement de maladies associées à la modulation du récepteur de glucocorticoïdes, et/ou à AP-1 et ou à l'activité de NF-KB, telles que des maladies inflammatoires et immunes, l'obésité et le diabète, ces composés ayant la structure de formule (I), l'invention concernant également les énantionères, les diastéréomères ou un sel pharmaceutiquement acceptable, ou un hydrate de ceux-ci, formule dans laquelle le groupe X représente O ou (Rx)(Ry); hétérocyclo ou hétéroaryle; E représente -N-, -NR1-, -O-, -C(=O), -S-, -SO2-, ou -CR2-; F représente -N-, -NR1a, -O-, -C(=O), -S-, -SO2-, ou -CR2a-; G représente indépendamment N, -NR1b-, -O-, -C(=O), -S-, -SO2- ou -CR2b-, à condition que le noyau hétérocyclique formé ne contienne pas une liaison S-S ou S-O t au moins un de E, F et G représentent un hétéroatome; et Ma, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, R4, R5a, R6, R7, X, Za et Z sont tels que définis dans la demande. L'invention concerne également des compositions pharmaceutiques et des méthodes de traitement de maladies associées inflammatoires ou immunes utilisant ces composés.