3,5-吡啶二羧酸,1,4-二氢-2-甲基-6-苯基-4-[(1E)-2-苯基乙烯基]-,二乙基酯 | 185259-16-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 中文名称: 3,5-吡啶二羧酸,1,4-二氢-2-甲基-6-苯基-4-[(1E)-2-苯基乙烯基]-,二乙基酯
• 英文名称: MRS 1097
• 英文别名: 3,5-diethyl-2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate；diethyl 6-methyl-2-phenyl-4-(2-phenylethenyl)-1,4-dihydro-3,5-pyridinedicarboxylate；3,5-diethyl 2-methyl-6-phenyl-4-[(E)-2-phenylethenyl]-1,4-dihydropyridine-3,5-dicarboxylate；diethyl 2-methyl-6-phenyl-4-[(E)-2-phenylethenyl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 185259-16-9
• 化学式: C₂₆H₂₇NO₄
• 分子量: 417.505
• InChiKey: XCXCNPNUEPMYRS-WUKNDPDISA-N

物化性质

• 熔点：
  123-124 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  566.6±50.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-吡啶二羧酸,1,4-二氢-2-甲基-6-苯基-4-[(1E)-2-苯基乙烯基]-,二乙基酯 在 四氯苯醌 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以29.8%的产率得到2-Methyl-6-phenyl-4-((E)-styryl)-pyridine-3,5-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  6-Phenyl-1,4-dihydropyridine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists

  摘要：

  An approach to designing dihydropyridines that bind to adenosine receptors without binding to L-type calcium channels has been described. 1,4-Dihydropyridine derivatives substituted with beta-styryl or phenylethynyl groups at the 4-position and aryl groups at the 6-position were synthesized and found to be selective for human A(3) receptors. Combinations of methyl, ethyl, and benzyl esters were included at the 3- and 5-positions. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxymethyl)phenyl]ethylamino]-5'-(N-ethyl carbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methycarbonyl)adenosine]. Structure-activity analysis indicated that substitution of the phenyl ring of the beta-styryl group but not of the 6-phenyl substituent was tolerated in A(3) receptor selective agents. Replacement of the 6-phenyl ring with a 3-thienyl or 3-furyl group reduced the affinity at A(3) receptors by 4- and g-fold, respectively. A 5-benzyl ester 4-trans-beta-styryl derivative, 26, with a K-i value of 58.3 nM at A(3) receptors, was >1700-fold selective vs either A(1) receptors or A(2A) receptors. Shifting the benzyl ester to the 3-position lowered the affinity at A(3) receptors 3-fold. A 5-benzyl, 3-ethyl ester 4-phenylethynyl derivative, 28, displayed a K-i value of 31.4 nM at A(3) receptors and 1300-fold selectivity vs A(1) receptors. The isomeric 3-benzyl, 5-ethyl diester was >600-fold selective for A(3) receptors. Oxidation of 28 to the corresponding pyridine derivative reduced affinity at A(3) receptors by 88-fold and slightly increased affinity at A(1) receptors.

  DOI：

  10.1021/jm960457c
• 作为产物：
  描述：

  ethyl (E)-3-phenyl-3-[(triphenyl-lambda5-phosphanylidene)amino]prop-2-enoate 、 ethyl 2-(3-phenylpropylene)acetoaceacetate 以 氯仿 为溶剂， 反应 30.0h， 以71%的产率得到3,5-吡啶二羧酸,1,4-二氢-2-甲基-6-苯基-4-[(1E)-2-苯基乙烯基]-,二乙基酯
  参考文献：
  名称：

  N-乙烯基磷腈与α，β-不饱和酮的反应，选择性合成β-氨基酸和氨基膦酸酯衍生的吡啶和二氢吡啶

  摘要：

  的反应Ñ与α-vinylic磷腈，β不饱和酮导致吡啶的形成从β氨基酸在一个区域选择性的方式得到。使用衍生自α-酰基苯乙烯基-羧酸酯或-膦酸酯的官能化烯酮提供了被羧酸酯或膦酸酯基团取代的生物活性不对称和对称二氢吡啶，包括硝苯地平，非洛地平，MRS 1097和依诺地平类似物。

  DOI：

  10.1016/j.tet.2007.03.146

文献信息

• 5-pyridyl-1, 3-azole compounds, process for producing the same and use there of
  申请人：Ohkawa Shigenori

  公开号：US20090048307A1

  公开（公告）日：2009-02-19

  An optionally N-oxidized compound represented by the formula: wherein R 1 represents hydrogen, hydrocarbon, heterocycle, amino, acyl, R 2 represents an aromatic group, R 3 represents hydrogen, pyridyl, aromatic hydrocarbon, X represents oxygen, optionally oxidized sulfur, Y represents a bond, an oxygen, optionally oxidized sulfur, a group represented by the formula NR 4 (R 4 represents hydrogen, hydrocarbon or acyl) and Z represents a bond or a divalent acyclic hydrocarbon, or a salt thereof has an excellent adenosine A 3 receptor antagonistic activity and is used as an agent for preventing or treating diseases related to an adenosine A 3 receptor. Furthermore, the compound (I) or a salt thereof has p38 MAP kinase inhibitory activity and TNF-α inhibitory activity and is used as an agent for preventing or treating diseases related to p38 MAP kinase and diseases related to TNF-α.

  一种可选择氧化的化合物，其化学式表示为：其中R1表示氢，碳氢化合物，杂环，氨基，酰基，R2表示芳香基团，R3表示氢，吡啶基，芳香烃，X表示氧，可选择氧化的硫，Y表示键，氧，可选择氧化的硫，一个由公式NR4（R4表示氢，碳氢化合物或酰基）表示的基团和Z表示键或二价无环碳氢化合物，或其盐具有出色的腺苷A3受体拮抗活性，并用作预防或治疗与腺苷A3受体相关的疾病的药剂。此外，该化合物（I）或其盐具有p38 MAP激酶抑制活性和TNF-α抑制活性，并用作预防或治疗与p38 MAP激酶和TNF-α相关的疾病的药剂。
• 5-PYRIDYL-1,3-AZOLE COMPOUNDS, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1180518B1

  公开（公告）日：2007-01-17
• Interaction of 1,4-Dihydropyridine and Pyridine Derivatives with Adenosine Receptors:  Selectivity for A₃ Receptors
  作者：A. Michiel van Rhee、Ji-long Jiang、Neli Melman、Mark E. Olah、Gary L. Stiles、Kenneth A. Jacobson

  DOI：10.1021/jm9600205

  日期：1996.1.1

  1,4-Dihydropyridine and pyridine derivatives bound to three subtypes of adenosine receptors in the micromolar range. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine]. Structure-activity analysis at adenosine receptors indicated that sterically bulky groups at the 4-, 5-, and 6-positions are tolerated. (R,S)-Nicardipine, 12, displayed K-i values of 19.6 and 63.8 mu M at rat A(1) and A(2A) receptors, respectively, and 3.25 mu M at human A(3) receptors. Similarly, (R)-niguldipine, 14, displayed K-i values of 41.3 and 1.90 mu M at A(1) and A(3) receptors, respectively, and was inactive at A(2A) receptors. A preference for the R- vs the S-enantiomer was observed for several dihydropyridines at adenosine receptors, in contrast with the selectivity at L-type Ca2+ channels. A 4-trans-beta-styryl derivative, 24, with a K-i value of 0.670 mu M at A(3) receptors, was 24-fold selective vs A(1) receptors (K-i = 16.1 mu M) and 74-fold vs A(2A) receptors (K-i = 49.3 mu M). The affinity of 24 at L-type Ca2+ channels, measured in rat brain membranes using [H-3]isradipine, indicated a K-i value of 0.694 mu M, and the compound is thus nonselective between A(3) receptors and L-type Ca2+ channels. Inclusion of a 6-phenyl group enhanced A(3) receptor selectivity: Compound 28 (MRS1097; 3,5-diethyl 2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate) was 55-fold selective vs A(1) receptors, 44-fold selective vs A(2A) receptors, and over 1000-fold selective vs L-type Ca2+ channels. In addition, compound 28 attenuated the A(3) agonist-elicited inhibitory effect on adenylylcyclase. Furthermore, whereas nicardipine, 12, displaced radioligand from the Na+-independent adenosine transporter with an apparent affinity of 5.36 +/- 1.51 mu M, compound 28 displaced less than 10% of total binding at a concentration of 100 mu M. Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A(3) adenosine antagonists.
• US7276527B2
  申请人：——

  公开号：US7276527B2

  公开（公告）日：2007-10-02
• 6-Phenyl-1,4-dihydropyridine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists
  作者：Ji-long Jiang、A. Michiel van Rhee、Neli Melman、Xiao-duo Ji、Kenneth A. Jacobson

  DOI：10.1021/jm960457c

  日期：1996.1.1

  An approach to designing dihydropyridines that bind to adenosine receptors without binding to L-type calcium channels has been described. 1,4-Dihydropyridine derivatives substituted with beta-styryl or phenylethynyl groups at the 4-position and aryl groups at the 6-position were synthesized and found to be selective for human A(3) receptors. Combinations of methyl, ethyl, and benzyl esters were included at the 3- and 5-positions. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxymethyl)phenyl]ethylamino]-5'-(N-ethyl carbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methycarbonyl)adenosine]. Structure-activity analysis indicated that substitution of the phenyl ring of the beta-styryl group but not of the 6-phenyl substituent was tolerated in A(3) receptor selective agents. Replacement of the 6-phenyl ring with a 3-thienyl or 3-furyl group reduced the affinity at A(3) receptors by 4- and g-fold, respectively. A 5-benzyl ester 4-trans-beta-styryl derivative, 26, with a K-i value of 58.3 nM at A(3) receptors, was >1700-fold selective vs either A(1) receptors or A(2A) receptors. Shifting the benzyl ester to the 3-position lowered the affinity at A(3) receptors 3-fold. A 5-benzyl, 3-ethyl ester 4-phenylethynyl derivative, 28, displayed a K-i value of 31.4 nM at A(3) receptors and 1300-fold selectivity vs A(1) receptors. The isomeric 3-benzyl, 5-ethyl diester was >600-fold selective for A(3) receptors. Oxidation of 28 to the corresponding pyridine derivative reduced affinity at A(3) receptors by 88-fold and slightly increased affinity at A(1) receptors.