2-氧代环己烷羧酸乙酯 | 1198-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烷
• 中文名称: 2-氧代环己烷羧酸乙酯
• 中文别名: 4-氧四氢-2H-硫代吡喃-3-羧酸乙酯
• 英文名称: ethyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate
• 英文别名: Ethyl 4-oxo-tetrahydrothiopyran-3-carboxylate；Ethyl tetrahydrothiopyran-4-one-3-carboxylate；ethyl 4-oxotetrahydrothiopyran-3-carboxylate；3-ethoxycarbonylthian-4-one；4-oxo-tetrahydro-thiopyran-3-carboxylic acid ethyl ester；4-Oxo-tetrahydro-thiopyran-3-carbonsaeure-aethylester；ethyl 4-oxothiane-3-carboxylate
• CAS: 1198-44-3
• 化学式: C₈H₁₂O₃S
• mdl: MFCD00040797
• 分子量: 188.247
• InChiKey: FXADJIANKOBZGT-UHFFFAOYSA-N

物化性质

• 熔点：
  59 °C
• 沸点：
  97-98 °C(Press: 0.1 Torr)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  2-氧代环己烷羧酸乙酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium carbonate 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 8-(4-(4-fluorophenoxy)phenyl)-3,4-dihydro-1H-thiopyrano[4,3-b]quinilin-10(5H)-one
  参考文献：
  名称：

  Optimization of 1,2,3,4-Tetrahydroacridin-9(10H)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships

  摘要：

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.

  DOI：

  10.1021/jm200015a
• 作为产物：
  描述：

  4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid ethyl ester 生成 2-氧代环己烷羧酸乙酯
  参考文献：
  名称：

  Bennett; Scorah, Journal of the Chemical Society, 1927, p. 199

  摘要：

  DOI：

文献信息

• Highly Efficient Access to Original Polycyclic Pyrrolopiperazine Scaffolds by a Three-Component Reaction with 1,3-Dicarbonyls
  作者：Thierry Constantieux、Jean Rodriguez、Frédéric Liéby-Muller

  DOI：10.1055/s-2007-973906

  日期：——

  Molecular sieves have been found to promote a new fast, environmentally friendly and experimentally simple multicomponent domino reaction from 1,3-dicarbonyls for the synthesis of pyrrolopiperazine and azasteroid-like scaffolds, of potential synthetic and biological interests.

  分子筛已被发现能够促进一种新颖的、快速且环境友好、实验操作简单的多组分多米诺反应，该反应以1,3-二羰基化合物为原料，合成具有潜在合成和生物学兴趣的吡咯并哌嗪及类似氮杂甾体骨架。
• Discovery of Novel Spiroindoline Derivatives as Selective Tankyrase Inhibitors
  作者：Fumiyuki Shirai、Takeshi Tsumura、Yoko Yashiroda、Hitomi Yuki、Hideaki Niwa、Shin Sato、Tsubasa Chikada、Yasuko Koda、Kenichi Washizuka、Nobuko Yoshimoto、Masako Abe、Tetsuo Onuki、Yui Mazaki、Chizuko Hirama、Takehiro Fukami、Hirofumi Watanabe、Teruki Honma、Takashi Umehara、Mikako Shirouzu、Masayuki Okue、Yuko Kano、Takashi Watanabe、Kouichi Kitamura、Eiki Shitara、Yukiko Muramatsu、Haruka Yoshida、Anna Mizutani、Hiroyuki Seimiya、Minoru Yoshida、Hiroo Koyama

  DOI：10.1021/acs.jmedchem.8b01888

  日期：2019.4.11

  pathway inhibition on tumor growth, we set out to find small-molecule inhibitors of TNKS/TNKS2 with suitable drug-like properties. Starting from 1a, a high-throughput screening hit, the spiroindoline derivative 40c (RK-287107) was discovered as a potent TNKS/TNKS2 inhibitor with >7000-fold selectivity against the PARP1 enzyme, which inhibits WNT-responsive TCF reporter activity and proliferation of human

  经典的WNT途径在癌症发病机理中起重要作用。据报道，抑制端粒聚合酶（TNKS / TNKS2）的聚（ADP-核糖）聚合酶催化活性可通过防止AXIN（Wnt /β的负调节剂）的多聚ADP-核糖基化依赖性降解来降低Wnt /β-catenin信号。 -catenin信号传导。为了研究tankyrase和Wnt途径抑制对肿瘤生长的影响，我们着手寻找具有类似药物性质的TNKS / TNKS2小分子抑制剂。从1a开始，它是一种高通量筛选命中物，螺环丝氨酸衍生物40c（RK-287107）被发现是一种有效的TNKS / TNKS2抑制剂，对PARP1酶的选择性> 7000倍，从而抑制了WNT响应的TCF报道分子的活性和增殖。人结肠直肠癌细胞系COLO-320DM的制备。在小鼠异种移植模型中，RK-287107还显示出剂量依赖性的肿瘤生长抑制作用。这些观察结果表明，RK-287107是一种有前途的先导化
• Struktur- und Konformations-Wirkungs-Beziehungen heterocyclischer Acetylcholinanaloga, 18. Mitt.1) Synthese und muskarinartige Wirkung von Estern des Sulfoarecaidins und Sulfoisoarecaidins
  作者：Ulrich Moser、Günter Lambrecht、Ernst Mustschler、Jan Sombroek

  DOI：10.1002/ardp.19833160805

  日期：——

  Es wurden Ester des Sulfoarecaidins und Sulfoisoarecaidins 5 und 6 synthetisiert und an der Longitudinalmuskulatur des Meerschweinchen‐Ileums auf muskarinartige Wirkung untersucht. Die Stärke der Muskarinwirkung der Ester 5 und 6 ist von der Länge der Esterseitenkette abhängig.

  合成了磺基异槟榔素和磺基异槟榔素 5 和 6 的酯，并检查了毒蕈碱对豚鼠回肠纵向肌肉的影响。酯5和6的毒蕈碱作用强度取决于酯侧链的长度。
• Synthesis and hypoglycemic activity of 7,8-dihydro-6H-thiopyrano(3,2-d)pyrimidine derivatives and related compounds.
  作者：SACHIO OHNO、KIYOSHI MIZUKOSHI、OSAMU KOMATSU、YASUO KUNOH、YOSHIKI NAKAMURA、EIICHI KATOH、MITSUAKI NAGASAKA

  DOI：10.1248/cpb.34.4150

  日期：——

  A series of 2-amino-7, 8-dihydro-4-piperazinyl- and 4-amino-7, 8-dihydro-2-piperazinyl-6H-thiopyrano[3, 2-d]pyrimidines and related compounds were synthesized and evaluated for hypoglycemic activity. Several compounds exhibited excellent activity, and 7, 8-dihydro-2-(4-methyl-piperazinyl)-4-(1-pyrrolidinyl)- (8c, dimaleate : MTP-1307) and 2-amino-7, 8-dihydro-4-piperazinyl-6H-thiopyrano[3, 2-d]pyrimidine (18a, dimaleate : MTP-1403) were selected for further investigation.Oral administration of 8c and 18a at 50 mg/kg markedly improved oral glucose tolerance in ob/ob mice. In this test, buformin also showed activity, whereas tolbutamide produced no significant improvement.

  合成了一系列2-氨基-7, 8-二氢-4-哌嗪基和4-氨基-7, 8-二氢-2-哌嗪基-6H-噻吡喃[3, 2-d]嘧啶及相关化合物，并评估了它们的降糖活性。 Several compounds exhibited excellent activity, and 7, 8-dihydro-2-(4-methyl-piperazinyl)-4-(1-pyrrolidinyl)- (8c, dimaleate: MTP-1307) 和 2-amino-7, 8-dihydro-4-piperazinyl-6H-thiopyrano[3, 2-d]pyrimidine (18a, dimaleate: MTP-1403) 被选为进一步研究的对象。在对 ob/ob 小鼠进行50 mg/kg的口服给药实验中，8c和18a显著改善了口服葡萄糖耐受性。在该实验中，布氟胺也显示出活性，而托吡胺并未产生显著改善。
• Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres
  作者：Per Sauerberg、Erik Falch、Eddi Meier、Hanne L. Lemboel、Povl Krogsgaard-Larsen

  DOI：10.1021/jm00402a010

  日期：1988.7

  oxotremorine M, pirenzepine, and quinuclidinyl benzilate as ligands and were supported by studies on the isolated guinea pig ileum. The degree of muscarinic agonist activity of the compounds (M-agonist index) and their selectivity for M-1 or M-2 muscarinic receptor subtypes (M-2/M-1 index) were estimated on the basis of receptor-binding studies. The in vitro pharmacological profiles of the compounds

  已经合成了许多构象受限的3-烷氧基-4,5,6,7-四氢异恶唑并[4,5-c]吡啶（O-烷基-THPO）型毒蕈碱激动剂的S-甲基ulf类似物。这些3-烷氧基-5-甲基-6,7-二氢-4H-硫代吡喃并[3,4-d]异恶唑-5-鎓（O-烷基-S-甲基-DHTO）类似物对毒蕈碱受体的影响（7a -d）在tri结合的奥曲莫林M，哌仑西平和苯甲酸奎宁环酯作为配体的受体结合实验中进行了评估，并得到了对分离的豚鼠回肠的研究的支持。在受体结合研究的基础上，估算了化合物的毒蕈碱激动剂活性的程度（M-激动剂指数）及其对M-1或M-2毒蕈碱受体亚型的选择性（M-2 / M-1指数）。将该化合物的体外药理学特征与槟榔碱及其are和3-甲氧基异恶唑等排体，磺基槟榔碱和O，5-二甲基-THPO分别进行了比较。尽管O-甲基-DHTO（5a）和N-甲基-DHTO（6a）处于非活性状态，但所有的sulf类似物7a-d均为毒