N¹,N¹-dimethyl-N³-phenylpropane-1,3-diamine | 13658-95-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹,N¹-dimethyl-N³-phenylpropane-1,3-diamine
• 英文别名: N,N-dimethyl-N'-phenyl-propane-1,3-diamine；N,N-dimethyl-N'-phenyl-1,3-propanediamine；N-[3-(dimethylamino)propyl]aniline；N,N-dimethyl-N'-phenyl-propanediyldiamine；N,N-Dimethyl-N'-phenyl-propandiyldiamin；1,3-Propanediamine, N,N-dimethyl-N'-phenyl-；N',N'-dimethyl-N-phenylpropane-1,3-diamine
• CAS: 13658-95-2
• 化学式: C₁₁H₁₈N₂
• 分子量: 178.277
• InChiKey: KHICLGAAEQIDSH-UHFFFAOYSA-N

物化性质

• 熔点：
  187-188 °C
• 沸点：
  83-84 °C(Press: 0.4 Torr)
• 密度：
  0.978±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2921590090

反应信息

• 作为反应物：
  描述：

  N¹,N¹-dimethyl-N³-phenylpropane-1,3-diamine 以 苯 为溶剂， 生成 2.2'-Dimethoxy-benzilsaeure-N-<γ-dimethylamino-propyl>-anilid
  参考文献：
  名称：

  Shklyaev,V.S.; Pantsurkin,V.I., Journal of Organic Chemistry USSR (English Translation), 1968, vol. 4, p. 279 - 284

  摘要：

  DOI：
• 作为产物：
  描述：

  3-氯-N-苯基丙酰胺 在 lithium aluminium tetrahydride 、 苯 作用下， 生成 N¹,N¹-dimethyl-N³-phenylpropane-1,3-diamine
  参考文献：
  名称：

  Chlorinated o-Dimethylaminopropylaminodiphenyl Sulfide Derivatives

  摘要：

  DOI：

  10.1021/jo01118a013

文献信息

• Halogen bonding enhances activity in a series of dual 5-HT₆/D₂ ligands designed in a hybrid bioisostere generation/virtual screening protocol
  作者：Jakub Staroń、Dawid Warszycki、Rafał Kurczab、Grzegorz Satała、Ryszard Bugno、Adam Hogendorf、Andrzej J. Bojarski

  DOI：10.1039/c6ra08714k

  日期：——

  Consequently, a series of derivatives of the found hit 1d (N-[2-(dimethylamino)ethyl]-N-(2-phenylethyl)aniline) was synthesized. The most active 5-HT6/D2 ligands also showed affinity for 5-HT7R and 5-HT2AR. The para-chloroaniline derivative was identified as a potent dual 5-HT6/5-HT7 receptor antagonist (Ki = 24 nM and Kb = 30 nM, Ki = 4 nM and Kb = 1.4 nM, respectively). In the case of halogen-containing

  通过与在第二个靶标上具有活性的化合物的相似性相结合的化学空间变窄与化学空间缩小相结合的新型杂化生物等排体生成/虚拟筛选方法已成功地用于开发结构新的双5-HT 6 / D 2受体配体。因此，合成了所发现的命中1d的一系列衍生物（N- [2-（二甲基氨基）乙基] -N-（2-苯基乙基）苯胺）。最活跃的5-HT 6 / d 2点的配体也显示出对5-HT 7 R和5-HT 2A R的对位-chloroaniline衍生物被鉴定为一种有效的双重5-HT 6 /5-HT7受体拮抗剂（ K i = 24 nM和K b = 30 nM， K i = 4 nM和K b = 1.4 nM）。对于含卤素的化合物，在5-HT 6，D 2和5-HT 7受体上观察到了有趣的结构-活性关系，随后使用结合了量子极化的分子模型方法研究了配体-受体复合物配体对接（QPLD）和分子力学通用出生/表面面积（MM / GBSA）自由能计算，可以确定假定的卤素结合口袋。
• Novel Derivatives of Benzo[<i>b</i>]thieno[2,3-<i>c</i>]quinolones:  Synthesis, Photochemical Synthesis, and Antitumor Evaluation
  作者：Jasna Dogan Koružnjak、Mira Grdiša、Neda Slade、Branimir Zamola、Krešimir Pavelić、Grace Karminski-Zamola

  DOI：10.1021/jm0210966

  日期：2003.10.1

  3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma

  苯并[b]噻吩并[2,3-c]喹诺酮类化合物3a-j的新型衍生物是从取代的苯并[b]噻吩-2-羰基氯化物到其相应的苯并[b]噻吩-2-起始的多步合成方法羧酰胺，将其光化学脱卤化氢生成相应的取代苯并[b]噻吩并[2,3-c]喹诺酮。通过在NaH存在下用3-二甲基氨基丙基氯烷基化由3i制备化合物4。从3g化合物5和6的多步合成中制备化合物7a，b。发现化合物3b，3c-f，3h，7a和7b对恶性细胞系具有抑制细胞生长的活性：胰腺癌（MiaPaCa2），乳腺癌（MCF7），宫颈癌（HeLa），喉癌（Hep2），结肠癌（CaCo-2），黑素瘤（HBL），人成纤维细胞系（WI-38）。在喹诺酮氮上带有3-二甲基氨基丙基取代基的化合物（3b，3c-f，3h）显示出比在酰胺氮上带有相同取代基的化合物（7a和7b）更高的抗肿瘤活性。具有在喹诺酮氮上的3-二甲基氨基丙基取代基和在位置9的甲氧基羰基取代基的化
• Synthesis, Photochemical Synthesis and Antitumor Evaluation of Novel Derivatives of Thieno[3',2':4,5]thieno[2,3-c]quinolones.
  作者：Jasna DoganKoruznjak、Neda Slade、Branimir Zamola、Kresimir Pavelic、Grace Karminski-Zamola

  DOI：10.1248/cpb.50.656

  日期：——

  The novel derivatives of thieno[3′,2′:4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a—c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a—c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a—d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3′,2′:4,5]thieno[2,3-c]quinolones 6a—d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibiedt marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.

  新合成的噻吩[3′,2′:4,5]噻吩[2,3-c]喹诺酮6a、6b、7、10a和10b通过多步合成法制备，起始原料为噻吩-3-羧醛和丙二酸，经过羟基醛缩合反应，或者从3-溴噻吩或甲基4-溴噻吩-2-羧酸酯通过赫克反应获得。它们最终得到相应的取代噻吩丙烯酸3a—c，这些产物进一步环化成噻吩[2,3-c]噻吩-2-氯甲酰基氯4a—c，并转化为噻吩[2,3-c]噻吩-2-羧酰胺5a—d。所制备的羧酰胺经过光化学脱卤化反应转化为相应的取代噻吩[3′,2′:4,5]噻吩[2,3-c]喹诺酮6a—d。化合物7是通过与N-[3-(二甲氨基)丙基]氯化氢在NaH存在下进行烷基化反应，从化合物6d制得的。化合物10a和10b则是从化合物6c经过对酸8和酸氯化物9的多步合成制得的。化合物6a、6b、7、10a和10b对多种恶性细胞系表现出细胞抑制活性，包括胰腺癌（MiaPaCa2）、乳腺癌（MCF7）、宫颈癌（HeLa）、喉癌（Hep2）、结肠癌（CaCo-2）、黑色素瘤（HBL）以及人纤维母细胞系（WI-38）。化合物6b在喹诺酮氮上有3-二甲氨基丙基取代基，9位有甲氧基羰基取代基，显示出显著的抗肿瘤活性。相反，化合物7虽然在喹诺酮氮上也有3-二甲氨基丙基取代基，但在9位则有苯胺取代基，表现出的抗肿瘤活性相对较低。
• Synthesis of Pyrimidine-Fused Benzazepines from 5-Allyl-4,6-dichloropyrimidines
  作者：Lina M. Acosta-Quintero、Jorge Jurado、Manuel Nogueras、Alirio Palma、Justo Cobo

  DOI：10.1002/ejoc.201500632

  日期：2015.8

  A detailed examination of the synthesis of functionalized 6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines 4 is described. Base-promoted aromatic nucleophilic substitution of 5-allyl-4,6-dichloropyrimidines 1a–c with different N-substituted anilines and indoline gave the corresponding aminolysis products 3a–p, which on acid-promoted intramolecular Friedel–Crafts cyclization produced the target polysubstituted

  描述了功能化 6,11-二氢-5H-苯并 [b] 嘧啶并 [5,4-f] 氮杂 4 合成的详细检查。用不同的 N-取代苯胺和二氢吲哚对 5-烯丙基-4,6-二氯嘧啶 1a-c 进行碱促进的芳香亲核取代得到相应的氨解产物 3a-p，在酸促进的分子内 Friedel-Crafts 环化作用下产生目标多取代6,11-二氢-5H-苯并[b]嘧啶并[5,4-f]氮杂4a-p，产率中等至极高。
• 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-ones
  申请人：IMPACT THERAPEUTICS, INC.

  公开号：US10703759B2

  公开（公告）日：2020-07-07

  Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

  所公开的是 8,9-二氢咪唑并[1,2-a]嘧啶并[5,4-e]嘧啶-5(6H)-酮化合物，具体由式 I 表示： 或其药学上可接受的盐或原药，其中 A 和 R1-R7 在此定义。具有式 I 的化合物是 Wee1 激酶抑制剂。因此，本公开的化合物可用于治疗由 Wee1 活性异常引起的疾病。