3-Ethoxycarbonyl-2-isothiocyanatopyridine | 128921-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-Ethoxycarbonyl-2-isothiocyanatopyridine
• 英文别名: Ethyl 2-isothiocyanatopyridine-3-carboxylate
• CAS: 128921-93-7
• 化学式: C₉H₈N₂O₂S
• mdl: MFCD25957575
• 分子量: 208.241
• InChiKey: NGFKXYJJJIMWRR-UHFFFAOYSA-N

物化性质

• 沸点：
  344.8±27.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  83.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Ethoxycarbonyl-2-isothiocyanatopyridine 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 生成 3-((S)-2-Hydroxy-1-methyl-ethyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  带有原酸酯基的杂环异硫氰酸酯与氨基醇的反应

  摘要：

  杂环异硫氰酸酯1,5,9，轴承的直径： -酯基团转化为硫脲衍生物2A-C，图6a-b ，和图10A-B ，分别使用β氨基醇，以及稠环体系，例如，噻吩并[3,2-d]嘧啶4a-b，吡啶并[2,3- d ]嘧啶8，蝶啶11a，噻唑并[3,2- a ]吡啶并[2,3 - d ]嘧啶7a-b和噻唑并[ 3，2- a ] mieno [3，2 - d ]吡啶3a-c衍生物。

  DOI：

  10.1002/jhet.5570350331
• 作为产物：
  描述：

  2-氨基烟酸乙酯 以 二氯甲烷 、 水 为溶剂， 以50%的产率得到3-Ethoxycarbonyl-2-isothiocyanatopyridine
  参考文献：
  名称：

  3-乙氧基羰基-2-异硫氰基氰基吡啶的合成和转化。吡啶并[2,3- d ]嘧啶和一些偶氮吡啶并[2,3- d ]嘧啶

  摘要：

  3-乙氧羰基-2-异硫氰基（2），由2-氨基-3- ethoxycarbonylpyridine（制备1由硫光气法），被转换成thiouretanes 3和4，1,4-二取代的氨基硫脲6，硫代酰胺8，和硫脲15和18。化合物2和3被转换成的双环吡啶并[2,3- d ]嘧啶5，9，10，11，12，16，和17，和三环azolopyrido [2,3- d ]嘧啶13和14。

  DOI：

  10.1002/jhet.5570270331

文献信息

• Synthesis of Thiazole and Fused Thiazolo Derivatives
  作者：Uro? Urleb、Richard Neidlein、Walter Kramer

  DOI：10.1002/hlca.19930760127

  日期：1993.2.10

  of thiazole and fused thiazolo derivatives 2–4, 6–8, 10a–11b, 13–16 from heterocylic isothiocyanates 1, 5, 9, and 12 bearing an ortho ester group and bifunctional reagents, such as substituted propargylamines, is described. Different regioselectivity of intramolecular nucleophilic attack of the thiourea S-atom on the C C bond, resulting in the formation of both thiazolo and thiazino derivatives, as

  的噻唑的合成和稠合的噻唑衍生物2 - 4，6 - 8，10A - 11B，13 - 16从杂环异硫氰酸酯1，5，9，和12承载的原酸酯基团和双官能团的试剂，如被取代的炔丙胺，描述。讨论了硫脲S原子对CC键的分子内亲核攻击的不同区域选择性，导致噻唑基和噻嗪基衍生物的形成，以及NMR结构的阐明。
• Discovery of a Novel 5-HT₃ Antagonist/5-HT_1A Agonist 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3<i>H</i>)-one (TZB-30878) as an Orally Bioavailable Agent for Irritable Bowel Syndrome
  作者：Akira Asagarasu、Teruaki Matsui、Hiroyuki Hayashi、Satoru Tamaoki、Yukinao Yamauchi、Kouichi Minato、Michitaka Sato

  DOI：10.1021/jm1002292

  日期：2010.11.11

  We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315-1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.
• High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships
  作者：Maria Modica、Maria Santagati、Filippo Russo、Carlo Selvaggini、Alfredo Cagnotto、Tiziana Mennini

  DOI：10.1016/s0223-5234(00)00175-6

  日期：2000.8

  In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT1AR. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT1A Ki 1 499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
• Urleb, Uros, Journal of Heterocyclic Chemistry, 1995, vol. 32, # 1, p. 69 - 72
  作者：Urleb, Uros

  DOI：——

  日期：——
• URLEB, UROS;STANOVNIK, BRANKO;TISLER, MIHA, J. HETEROCYCL. CHEM., 27,(1990) N, C. 643-646
  作者：URLEB, UROS、STANOVNIK, BRANKO、TISLER, MIHA

  DOI：——

  日期：——