6-amino-3,3-dimethyl-8-sulfanylidene-1H,3H,4H,8H-thiopyrano[3,4-c]pyran-5-carbonitrile | 155473-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 碳二硫内酯
• 英文名称: 6-amino-3,3-dimethyl-8-sulfanylidene-1H,3H,4H,8H-thiopyrano[3,4-c]pyran-5-carbonitrile
• 英文别名: 6-amino-3,3-dimethyl-8-thioxo-4,8-dihydro-1H,3H-thiopyrano[3,4-c]pyran-5-carbonitrile；6-amino-5-cyano-3,3-dimethyl-8-thioxo-1,3,4,8-tetrahydrothiopyrano[3,4-c]pyran；6-amino-3,3-dimethyl-8-sulfanylidene-1,4-dihydrothiopyrano[3,4-c]pyran-5-carbonitrile
• CAS: 155473-85-1
• 化学式: C₁₁H₁₂N₂OS₂
• mdl: MFCD00450008
• 分子量: 252.361
• InChiKey: TZABRSKNZQQCGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-3,3-dimethyl-8-sulfanylidene-1H,3H,4H,8H-thiopyrano[3,4-c]pyran-5-carbonitrile 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 3,3-Dimethyl-6-methylsulfanyl-8-morpholin-4-yl-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile
  参考文献：
  名称：

  Synthesis and antibacterial activity of pyrano-(thiopyrano)[3,4-c]pyridine-, 2,7-naphthyridine-, and 5,6,7,8-tetrahydro-isoquinoline-3(2h)-thione derivatives

  摘要：

  DOI：

  10.1007/bf00780403
• 作为产物：
  描述：

  四氢-2 2-二甲基-4H-吡喃-4-酮 、 二硫化碳 、 丙二腈 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以88.3%的产率得到6-amino-3,3-dimethyl-8-sulfanylidene-1H,3H,4H,8H-thiopyrano[3,4-c]pyran-5-carbonitrile
  参考文献：
  名称：

  基于稠合吡啶硫酮的肼衍生物合成四环噻吩并三唑并吡啶

  摘要：

  开发了一种基于脂环酮和杂环酮的稠合吡啶硫酮肼衍生物的合成方法。对这些肼衍生物进行连续杂环化以获得三环三唑并[4,3- a ]吡啶、四环噻吩并[3,2 -e ][1,2,4]三唑并[ 4,3- a ]的新衍生物]吡啶，以及噻吩并[2,3 - c ][1,2,4]三唑并[3,4- a ]-2,7-萘啶的新杂环体系。

  DOI：

  10.1007/s11172-022-3503-5

文献信息

• Synthesis and biological activity of pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine derivatives as novel and potent phosphodiesterase type 4 inhibitors
  作者：Joan Taltavull、Jordi Serrat、Jordi Gràcia、Amadeu Gavaldà、Mònica Córdoba、Elena Calama、José Luis Montero、Míriam Andrés、Montserrat Miralpeix、Dolors Vilella、Begoña Hernández、Jorge Beleta、Hamish Ryder、Lluís Pagès

  DOI：10.1016/j.ejmech.2011.07.054

  日期：2011.10

  A series of pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines (PFP) were synthesized and tested for phosphodiesterase type 4 (PDE4) inhibitory activity, with the potential to treat asthma and chronic obstructive pulmonary disease (COPD). Structure–activity relationships within this series, leading to an increase of potency on the enzyme, is presented. Both gem-dimethylcyclohexyl moieties fused to the pyridine

  合成了一系列吡啶并[3'，2'：4,5]呋喃[3,2-d]嘧啶（PFP），并测试了其对4型磷酸二酯酶（PDE4）的抑制活性，具有治疗哮喘和慢性阻塞性疾病的潜力肺部疾病（COPD）。介绍了该系列中的结构-活性关系，从而增加了酶的效力。 既宝石稠合到吡啶环和在PFP骨架的5位上的取代-dimethylcyclohexyl部分，被证明是为了得到在酶的亲和性高的关键要素。
• Synthesis and Biological Activity of Pyrido[3′,2′:4,5]thieno[3,2-<i>d</i>]pyrimidines as Phosphodiesterase Type 4 Inhibitors
  作者：Joan Taltavull、Jordi Serrat、Jordi Gràcia、Amadeu Gavaldà、Míriam Andrés、Mònica Córdoba、Montserrat Miralpeix、Dolors Vilella、Jorge Beleta、Hamish Ryder、Lluís Pagès

  DOI：10.1021/jm100524j

  日期：2010.10.14

  A series of pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines (PTP) has been synthesized and tested as phosphodiesterase IV inhibitors (PDE4), a target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Structure−activity relationships within this series, leading to an increase of potency on the enzyme, are presented. The gem-dimethylcycloalkyl moiety fused to the pyridine ring proved

  合成了一系列吡啶并[3'，2'：4,5]噻吩并[3,2- d ]嘧啶（PTP）并作为磷酸二酯酶IV抑制剂（PDE4）进行了测试，这是治疗哮喘和慢性阻塞性疾病的靶标肺部疾病（COPD）。介绍了该系列中的结构活性关系，从而导致了酶效力的提高。为了在酶中获得更高的亲和力，与吡啶环稠合的宝石-二甲基环烷基被证明是支架的关键元素。
• Characterization of a Novel Pyranopyridine Inhibitor of the AcrAB Efflux Pump of Escherichia coli
  作者：Timothy J. Opperman、Steven M. Kwasny、Hong-Suk Kim、Son T. Nguyen、Chad Houseweart、Sanjay D'Souza、Graham C. Walker、Norton P. Peet、Hiroshi Nikaido、Terry L. Bowlin

  DOI：10.1128/aac.01866-13

  日期：2014.2

  Members of the resistance-nodulation-division (RND) family of efflux pumps, such as AcrAB-TolC of Escherichia coli , play major roles in multidrug resistance (MDR) in Gram-negative bacteria. A strategy for combating MDR is to develop efflux pump inhibitors (EPIs) for use in combination with an antibacterial agent. Here, we describe MBX2319, a novel pyranopyridine EPI with potent activity against RND efflux pumps of the Enterobacteriaceae . MBX2319 decreased the MICs of ciprofloxacin (CIP), levofloxacin, and piperacillin versus E. coli AB1157 by 2-, 4-, and 8-fold, respectively, but did not exhibit antibacterial activity alone and was not active against AcrAB-TolC-deficient strains. MBX2319 (3.13 μM) in combination with 0.016 μg/ml CIP (minimally bactericidal) decreased the viability (CFU/ml) of E. coli AB1157 by 10,000-fold after 4 h of exposure, in comparison with 0.016 μg/ml CIP alone. In contrast, phenyl-arginine-β-naphthylamide (PAβN), a known EPI, did not increase the bactericidal activity of 0.016 μg/ml CIP at concentrations as high as 100 μM. MBX2319 increased intracellular accumulation of the fluorescent dye Hoechst 33342 in wild-type but not AcrAB-TolC-deficient strains and did not perturb the transmembrane proton gradient. MBX2319 was broadly active against Enterobacteriaceae species and Pseudomonas aeruginosa . MBX2319 is a potent EPI with possible utility as an adjunctive therapeutic agent for the treatment of infections caused by Gram-negative pathogens.

  摘要 抗性-结节-分裂（RND）外排泵家族的成员，如大肠杆菌的 AcrAB-TolC 大肠杆菌 等外排泵家族成员在革兰氏阴性细菌的多药耐药性（MDR）中发挥着重要作用。对抗 MDR 的一种策略是开发与抗菌剂联合使用的外排泵抑制剂 (EPI)。在此，我们介绍了 MBX2319，这是一种新型吡喃吡啶 EPI，对肠杆菌科细菌的 RND 外排泵具有强效活性。 肠杆菌科 .MBX2319 降低了环丙沙星（CIP）、左氧氟沙星和哌拉西林对大肠杆菌的 MICs。 大肠杆菌 AB1157 的 MIC 值分别降低了 2 倍、4 倍和 8 倍，但并未单独表现出抗菌活性，对 AcrAB-TolC 缺失菌株也没有活性。MBX2319 （3.13 μM）与 0.016 μg/ml CIP（最小杀菌量）结合使用，可降低大肠杆菌的存活率（CFU/ml）。 大肠杆菌 与单独使用 0.016 μg/ml CIP 相比，暴露 4 小时后，大肠杆菌 AB1157 的存活率（CFU/ml）降低了 10,000 倍。与此相反，已知的 EPI 苯基精氨酸-β-萘胺（PAβN）在浓度高达 100 μM 时并没有提高 0.016 μg/ml CIP 的杀菌活性。MBX2319 增加了野生型而非 AcrAB-TolC 缺陷菌株中荧光染料 Hoechst 33342 的细胞内积累，但并未扰乱跨膜质子梯度。MBX2319 对 肠杆菌科 和 铜绿假单胞菌 .MBX2319 是一种强效 EPI，可用作治疗革兰氏阴性病原体感染的辅助治疗药物。
• Pyridothienopyrimidine Derivatives
  申请人：Pages Santacana Luis Miguel

  公开号：US20080207645A1

  公开（公告）日：2008-08-28

  A pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt or N-oxide thereof are disclosed, as well as pharmaceutical compositions comprising said compounds and methods of treatment or prevention of a pathological condition or disease susceptible to amelioration by inhibition of phosphodiesterase 4 using said compounds are disclosed.

  本发明公开了一种式(I)的吡啶并[3',2':4,5]噻吩并[3,2-d]嘧啶衍生物，或其药学上可接受的盐或N-氧化物，以及包括所述化合物的制药组合物和使用所述化合物抑制磷酸二酯酶4来治疗或预防病理状态或疾病的方法。
• Pyrido[3' ,2':4,5]Furo[3,2-d]Pyrimidine Derivatives
  申请人：Taltavull Moll Joan

  公开号：US20080221096A1

  公开（公告）日：2008-09-11

  The present disclosure relates to a pyridofuropyrimidine derivative of formula (I): wherein G 1 is a group chosen from —CR 6 R 7 — and —O— wherein R 6 and R 7 are independently chosen from hydrogen atoms and C 1-4 alkyl groups; R 1 and R 2 are independently chosen from hydrogen atoms and C 1-4 alkyl groups; R 3 is chosen from C 1-4 alkyl, C 1-4 alkoxy, amino, hydroxy, mono-C 1-4 alkylamino, di-C 1-4 alkylamino, C 3-8 cycloalkylamino, aryl, heteroaryl and saturated N-containing heterocyclyl groups which are bound to the pyridine ring through their nitrogen atom, all of them being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy, C 1-4 alkyl, C 1-4 alkoxy-C 1-4 alkyl, aryl-C 1-4 alkyl, —O(CO)OR 8 , C 1-4 alkoxy, —(CO)NR 8 R 9 , —CN, —CF 3 , —NR 8 R 9 , —SR 8 and —SO 2 NH 2 groups wherein R 8 and R 9 are each independently chosen from a hydrogen atom or a C 1-4 alkyl group; R 4 and R 5 are independently chosen from hydrogen atoms, C 1-4 alkyl groups, hydroxyl-C 1-4 alkyl groups and groups of formula (II): wherein p and q are integers chosen from 0, 1, 2 and 3; A is either a direct bond or a group chosen from —CONR 14 —, —NR 14 CO—, —O—, —COO—, —OCO—, —S—, —SO— and —SO 2 —, wherein each R 10 , R 11 , R 12 , R 13 and R 14 are independently chosen from a hydrogen atom and a C 1-4 alkyl group and G 2 is chosen from aryl, heteroaryl and heterocyclyl groups; wherein the group G 2 is optionally substituted by one or more substituents chosen from halogen atoms and C 1-4 alkyl, hydroxy, oxo, C 1-4 alkoxy-C 1-4 alkyl, aryl-C 1-4 alkyl, —(CO)OR 16 , C 1-4 alkoxy, —(CO)NR 16 R 17 , —CN, —CF 3 , —NR 16 R 17 —SR 16 and —SO 2 NH 2 groups; wherein R 16 and R 17 each independently chosen from hydrogen atom and a C 1-4 alkyl group and the pharmaceutically acceptable salts and N-oxides thereof.

  本公开涉及一种式为(I)的吡啶并呋喃嘧啶衍生物： 其中G1是从—CR6R7—和—O—中选择的基团，其中R6和R7分别选择自氢原子和C1-4烷基基团；R1和R2分别选择自氢原子和C1-4烷基基团；R3选择自C1-4烷基、C1-4烷氧基、氨基、羟基、单C1-4烷基氨基、双C1-4烷基氨基、C3-8环烷基氨基、芳基、杂芳基和饱和N-含杂环基团，它们通过它们的氮原子与吡啶环相连，所有这些基团都可以被一个或多个取代基取代，所述取代基选择自卤素原子和羟基、C1-4烷基、C1-4烷氧基-C1-4烷基、芳基-C1-4烷基、—O(CO)OR8、C1-4烷氧基、—(CO)NR8R9、—CN、—CF3、—NR8R9、—SR8和—SO2NH2基团，其中R8和R9各自选择自氢原子或C1-4烷基基团；R4和R5分别选择自氢原子、C1-4烷基基团、羟基-C1-4烷基基团和式(I)的基团： 其中p和q是选择自0、1、2和3的整数；A是直接键或从—CONR14—、—NR14CO—、—O—、—COO—、—OCO—、—S—、—SO—和—SO2—中选择的基团，其中每个R10、R11、R12、R13和R14各自选择自氢原子和C1-4烷基基团，G2选择自芳基、杂芳基和含杂环基团；其中基团G2可以被选择自卤素原子和C1-4烷基、羟基、氧代、C1-4烷氧基-C1-4烷基、芳基-C1-4烷基、—(CO)OR16、C1-4烷氧基、—(CO)NR16R17、—CN、—CF3、—NR16R17—SR16和—SO2NH2基团的一个或多个取代基取代；其中R16和R17各自选择自氢原子和C1-4烷基基团，以及其药学上可接受的盐和N-氧化物。