3-(6-chloro-pyridin-3-yl)-2,2-dimethyl-3-phenyl-propionic acid methyl ester | 1025482-51-2

• 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: 3-(6-chloro-pyridin-3-yl)-2,2-dimethyl-3-phenyl-propionic acid methyl ester
• 英文别名: methyl 3-(6-chloropyridin-3-yl)-2,2-dimethyl-3-phenylpropanoate
• CAS: 1025482-51-2
• 化学式: C₁₇H₁₈ClNO₂
• 分子量: 303.788
• InChiKey: IWTDKPVUUHWBDV-UHFFFAOYSA-N

物化性质

• 沸点：
  415.4±40.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(6-chloro-pyridin-3-yl)-2,2-dimethyl-3-phenyl-propionic acid methyl ester 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 palladium on activated charcoal 、 氢气 、 锌 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.5h， 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：

  6-chloro-α-phenyl-3-pyridinemethanol 在 4-二甲氨基吡啶 、 四氯化钛 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-(6-chloro-pyridin-3-yl)-2,2-dimethyl-3-phenyl-propionic acid methyl ester
  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-KAPPABETA ACTIVITY AND USE THEREOF
  申请人：Yang Bingwei Vera

  公开号：US20100004219A1

  公开（公告）日：2010-01-07

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory or immune associated diseases or disorders having the structure of formula I or an enantiomer, diastereomer, tautomer, or a pharmaceutically-acceptable salt, thereof, wherein: A is a 5-, 6-, or 7-membered heterocyclo or heteroaryl, each containing 1, 2, or 3 heteroatoms selected from N, O, and S and substituted with one to four groups, R 1 , R 2 , R 3 , and/or R 4 , provided that (i) A is not tetrazole or (ii) if A is thienyl or furanyl then Z is selected from a group other than succinimido or thalimido; M is selected from alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl; Ma is a linker between C and M and is selected from a bond and C 1 -C 3 alkylene; Q is selected from (i) hydrogen, halogen, nitro, cyano, hydroxy, C 1 -4alkyl, and substituted C 1 -4 alkyl; or (ii) Q is combined with R6 and with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO 2 , and N which ring may be optionally substituted with 0-2 R 5 groups or carbonyl; and Z is selected from alkyl, CF 3 , OH, cycloalkyl, heterocyclo, aryl, heteroaryl, —C(═O)NR 8 R 9 , —C(═O)R 8 , —C(NCN)NR 8 R 9 , —C(═O)OR 8 , —SO 2 R 8 , and —SO2NR8R9. M a , Z a , R 1 , R 2 , R 3 , R5 a , R 6 , R 7 , R 8 , R 9 and R 22 are as defined herein. Also provided are pharmaceutical compositions, combinations and methods of treating metabolic and inflammatory or immune associated diseases or disorders using said compounds.

  本发明提供了一些新型非甾体化合物，其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，包括代谢和炎症或免疫相关疾病或障碍。该化合物具有公式I或其对映异构体、顺反异构体、互变异构体或药学上可接受的盐，其中：A是5、6或7元杂环或杂环芳基，每个都含有1、2或3个从N、O和S中选择的杂原子，并取代有1至4个基团R1、R2、R3和/或R4，但（i）A不是四氮唑或（ii）如果A是噻吩基或呋喃基，则Z是选择自除琥珀酰亚胺或萘酰亚胺之外的一组；M选择自烷基、环烷基、芳基、杂环烷和杂环芳基；Ma是C和M之间的连接器，选择自键和C1-C3烷基；Q选择自（i）氢、卤素、硝基、氰基、羟基、C1-4烷基和取代的C1-4烷基；或（ii）Q与R6以及它们附着的碳原子结合形成3-至6元环烷基；或（iii）Q和M与它们附着的碳原子结合形成3-至7元环，其中包含1-2个杂原子，这些杂原子独立地选择自O、S、SO2和N的群，该环可以选择性地取代0-2个R5基团或羰基；Z选择自烷基、CF3、OH、环烷基、杂环烷基、芳基、杂环芳基、-C（=O）NR8R9、-C（=O）R8、-C（NCN）NR8R9、-C（=O）OR8、-SO2R8和-SO2NR8R9。Ma、Za、R1、R2、R3、R5a、R6、R7、R8、R9和R22的定义如本文所述。还提供了使用所述化合物的制药组合物和治疗代谢和炎症或免疫相关疾病或障碍的方法。
• 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。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1 AND/OR NF-KAPPAB ACTIVITY AND USE THEREOF
  申请人：Bristol-Myers Squibb Company

  公开号：EP2078015B1

  公开（公告）日：2012-03-21
• 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