2-dimethylaminoethyl acetoacetate | 6131-49-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 2-dimethylaminoethyl acetoacetate
• 英文别名: acetoacetic acid 2-dimethylamino-ethyl ester；2-(Dimethylamino)ethyl 3-oxobutanoate
• CAS: 6131-49-3
• 化学式: C₈H₁₅NO₃
• 分子量: 173.212
• InChiKey: LWFQGLZKTGSAQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-dimethylaminoethyl acetoacetate 在 氨 作用下， 以 乙醇 为溶剂， 生成 (Z)-3-Amino-but-2-enoic acid 2-dimethylamino-ethyl ester
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 9. Structure activity relationships around amlodipine

  摘要：

  The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated. Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor. Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituent and the DHP receptor. Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity.

  DOI：

  10.1016/0223-5234(91)90132-7
• 作为产物：
  描述：

  N,N-二甲基乙醇胺 、 2,2,6-三甲基-4H-1,3-二英-4-酮 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 以83%的产率得到2-dimethylaminoethyl acetoacetate
  参考文献：
  名称：

  1,4-DIHYDRO-NAPHTHYRIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION AND USE THEREOF

  摘要：

  本文披露了1,4-二氢-萘啶衍生物及其药物组合物和用途。1,4-二氢-萘啶衍生物是一种能够抑制乙酰胆碱酯酶活性并通过钙通道阻止细胞外钙流入细胞的化合物，即具有双重活性，对于制备用于治疗心血管疾病、脑血管疾病和痴呆症的药物具有潜在重要性。

  公开号：

  US20140364443A1

文献信息

• Organic Nitrates II[1]. Synthesis and Biological Activities of 4-Nitrooxymethylphenyl-1,4-dihydropyridines
  作者：Jochen Lehmann、Rainer Kahlich、Christoph Meyer Zum Gottesberge、Uwe Fricke

  DOI：10.1002/ardp.19973300804

  日期：——

  Both 2‐nitrooxymethyl‐4‐phenyl‐ (2) and 4‐nitrooxymethylphenyl‐1,4‐dihydropyridines (3) represent new combinations of two different vasodilating structures. 2 could not be isolated due to its spontaneous lactonization. Derivatives of 3 were obtained via Hantzsch synthesis using nitrooxymethylated benzaldehydes. The inotropic potency in isolated porcine trabecular muscles and the vasodilator activity

  2-硝基氧甲基-4-苯基-(2)和4-硝基氧甲基苯基-1,4-二氢吡啶(3)都代表了两种不同血管舒张结构的新组合。2由于其自发内酯化而无法分离。使用硝基氧甲基化苯甲醛通过 Hantzsch 合成获得 3 的衍生物。测定了离体猪小梁肌中的正性肌力效力和四种硝基氧苯基二氢吡啶在离体猪冠状动脉中的血管扩张活性。尼群地平 (NTD) 和三硝酸甘油酯 (GTN) 用作参考。3 是负性肌力，然而，小于 NTD 并且 - 除了二氰基衍生物 3d - 大于 GTN。血管扩张剂的特性不如尼群地平和 GTN 明显。血管选择性低。
• Acetoacetylation with Diketene Catalyzed by 4-Dimethylaminopyridine
  作者：Abraham Nudelman、Rachel Kelner、Neomi Broida、Hugo E. Gottlieb

  DOI：10.1055/s-1989-27260

  日期：——

  A useful procedure for the acetoacetylation of alcohols 1 with diketene 2 to acetoacetic esters 3 is reported.

  报道了一种有效的方法，将醇1与双酮烯酮2进行乙酰乙酰化反应，生成乙酰乙酸酯3。
• Syntheses, Calcium Channel Antagonist and Anticonvulsant Activities of Substituted 1,4-Dihydro-3,5-pyridinedicarboxylates Containing Various 3-Alkyl Ester Substituents
  作者：Sai-Hay Yiu、Edward E. Knaus

  DOI：10.1002/ardp.19973300109

  日期：——

  5‐pyridinedicarboxylates 10–20 containing an amine, quaternary ammonium, aryl(heteroaryl)alkenyl, 4 ‐ (4‐fluorophenyl)‐piperazin‐1‐yl or methoxy moiety in the C‐3 alkyl ester R‐substituent in combination with a C‐4 phenyl ring bearing a 2,3‐Cl2, 3‐NO2, 3‐NMe2, 4‐NMe2 or 3,4,5‐(OMe)3 X‐substituent were prepared using the Hantzsch 1,4‐dihydropyridine reaction. In vitro calcium channel antagonist activity (CCA)

  一组 3-烷基 5-异丙基 4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯 10-20 含有胺、季铵、芳基（杂芳基）烯基、4-（4 -氟苯基) -哌嗪 - C-3烷基酯R-取代基中的1-基或甲氧基部分与带有2,3-Cl2、3-NO2、3-NMe2、4-NMe2的C-4苯环组合或 3,4,5- (OMe) 3 X- 取代基使用 Hantzsch 1,4-二氢吡啶反应制备。使用豚鼠回肠纵向平滑肌测定法测定体外钙通道拮抗剂活性(CCA)。在C-4 3-硝基苯基系列化合物中，C-3酯R-取代基是CCA活性的决定因素，其中相对效力顺序为-CH2CH2CH=C-(2-甲基苯基)2±-CH2CH2NMe2.HCl>- CH2CH2CH = C-(3-甲基-2-噻吩基) 2> -CH2CH2 + NMe3 I-。C-4苯基X-取代基的位置和性质也是CCA活性的决定因素，其中相对活性顺序为3-NMe2>4-NMe2>3
• NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Oncostellae, S.L.

  公开号：EP3480201A1

  公开（公告）日：2019-05-08

  The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.

  本发明涉及一种新型的二氢吡啶衍生物，其化学式为(I)：作为选择的核受体调节剂，所述核受体包括雄激素受体和糖皮质激素受体，以及其制备方法，包括所述化合物的制药组合物和利用所述化合物制造用于治疗可以通过调节雄激素受体和/或糖皮质激素受体改善的病理情况或疾病的药物，所述病理情况或疾病包括癌症、转移性癌症、良性前列腺增生、多囊卵巢综合征（PCOS）、脱发、多毛症、痤疮、性腺功能减退、肌肉消耗性疾病、虚弱、库欣综合征、抗精神病药物诱导的体重增加、肥胖、创伤后应激障碍和酗酒。
• Calcium channel blocking and positive inotropic activities of ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-aryl-3-pyridinecarboxylate and analogs. Synthesis and structure-activity relationships
  作者：Ila Sircar、Eva K. Gregor、K. R. Anderson、Stehen J. Haleen、Yu Hsin Shih、Ronald E. Weishaar、Robert P. Steffen、Thomas A. Pugsley、M. D. Taylor

  DOI：10.1021/jm00111a047

  日期：1991.7

  The synthesis and pharmacological evaluation of a series of 2-[(arylsulfonyl)methyl]-4-aryl-5-cyano-1,4-dihydropyridine-3-carboxylic acid esters and analogues are described. These compounds possess a unique profile namely, calcium channel blocking and positive inotropic activities in vitro. Compound 54 was selected as the best compound in the series and was studied in detail. The synthesis and biological

  描述了一系列2-[（（芳基磺酰基）甲基] -4-芳基-5-氰基-1,4-二氢吡啶-3-羧酸酯和类似物的合成和药理学评价。这些化合物具有独特的特性，即钙通道阻滞和体外正性肌力活性。选择化合物54作为该系列中最好的化合物，并进行了详细研究。还报道了54种对映异构体的合成和生物学特征。数据表明，尽管54的钙通道阻滞特性是立体定向的，但正性肌力活性不是。描述和评价了3-和6-氰基和其他紧密相关的1,4-二氢吡啶衍生物的实例以进行比较，发现它们没有上述双重活性。