116170-90-2Relevant articles and documents
Determinative role of ring size and substituents in highly selective synthesis of functionalized bicyclic guanidine and tetra substituted thiophene derivatives based on salt adducts afforded by cyclic thioureas and ketene dithioacetal
Alizadeh, Abdolali,Vahabi, Amir Hossein,Bazgir, Ayoob,Khavasi, Hamid Reza,Zhu, Zhe,Zhu, Long-Guan
, p. 1342 - 1350 (2016)
The condensation of organic salt adducts generated by cyclic thioureas and 2-di(methylsulfanyl)methylenemalononitrile with dialkyl acetylenedicarboxylates selectively leads to either tetrasubstituted thiophenes (2 examples) or hitherto unreported bicyclic guanidine (13 examples) derivatives, with controlling factors being ring size, the substituent on the S-methylisothiourea and the bulk of the substituent on the dialkyl acetylenedicarboxylates. Green solvents, short reaction time; easy purification, high yield and selectivity, are key feature of this protocol in the condensation step. The performances of the reactions in the presence of free-base and a catalyst at room temperature is unprecedented in the synthesis of thiophene frameworks and functionalized bicyclic guanidine scaffolds.
Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity
Chen, Rui,Gong, Guowei,Han, Yufei,Lei, Qiancheng,Liao, Weike,Liu, Jiaan,Qi, Yinliang,Sun, Ming,Tang, Lei,Tian, Ye,Wang, Zhongyuan,Xie, Juan,Zhao, Yanfang
, (2020)
Using a rational design strategy for isoform-selective inhibition of PI3Kα, two series of novel 2,3,4,5-tetra-substituted thiophene derivatives containing either diaryl urea or N-Acylarylhydrazone scaffold were designed and synthesized. The most promising compound 12k was demonstrated to bear nanomolar PI3Kα inhibitory potency with 12, 28, 30, 196-fold selectivity against isoforms β, γ, δ and mTOR. Besides, it also showed good developability profiles in cell-based proliferation against a panel of human tumor cells as well as ADME assays. We herein report on their design, synthesis, SAR and potential developability properties.
Highly mild approach towards synthesis of tetrasubstituted thiophenes by an organic salt afforded by cyclic thioureas and ketene dithioacetals
Alizadeh, Abdolali,Vahabi, Amir Hossein,Bazgir, Ayoob,Khavasi, Hamid Reza,Zhu, Zhe,Ng, Seik Weng
, p. 85028 - 85034 (2015)
An organic salt generated by cyclic thioureas and 2-di(methylsulfanyl)methylene malononitrile in reaction with primary and secondary α-haloketones leads to tetrasubstituted thiophenes without using additional base or catalyst at room temperature. The S-methylisothiourea moiety of this salt as an organocatalyst performs a hybrid function of thiourea and imidazole to activate electrophiles via H-bonding and trigger cyclization via Lewis basicity character, respectively. Interestingly, a green solvent (in two step mode), short reaction time, easy purification, high yield and selectivity accompany this protocol. The structures of the intermediate and afforded adducts are fully characterized by analytical investigations and X-ray crystallography.
Reactions of ketene dithioacetal for a new versatile synthesis of 4,5-substituted 3-aminothiophene-2-carboxylate derivatives
Chavan, Satish M.,Toche, Raghunath B.,Patil, Vasant M.,Aware, Pankaj B.,Patil, Poonam S.
, p. 426 - 437 (2016)
ABSTRACT: Poly substituted 3-aminothiophenes were successfully synthesized in good yields by using a one-pot protocol via ketene S,S-acetal as an intermediate in basic medium (K2CO3/N,N-dimethylformamide) followed by Dieckmann condensation with ethyl bromoacetate. Further, chemistry of thiophenes was explored using active functional groups such as C3–NH2, C4–CN and C5–SCH3 on the thiophene nucleus. Synthesis of ethyl 3-acetamido-4-cyano-5-(methylthio)thiophene-2-carboxylate derivatives and ethyl 3-amino-4-carbamoyl-5-(methylthio)thiophene-2-carboxylate derivatives.
Preparation method and use of thiophene compound
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Paragraph 0107; 0108, (2020/02/17)
The invention belongs to the technical field of pharmaceutical chemistry, and relates to thiophene compounds shown by general formula I, pharmaceutically acceptable salts, solvates or prodrugs and preparation methods thereof. In which substituents L, Ar, R have the meanings given in the specification. The invention also relates to a strong PI3K inhibitory effect of a compound of the general formula I, and also relates to the use of such compounds and pharmaceutically acceptable salts, solvates or prodrugs thereof in the preparation of drugs for the treatment and/or prevention of diseases caused by abnormally high expression of PI3K, in particular in the preparation of drugs for the treatment and/or prevention of cancer.
NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts
Luo, Laichun,Meng, Lanlan,Sun, Qi,Ge, Zemei,Li, Runtao
supporting information, p. 259 - 263 (2014/01/06)
A NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts has been developed under mild conditions. This transformation involves sequential bromination/SN
Synthesis of new 1,2,4-oxadiazolidin-5-ylthiophenes and thienopyrimidine derivatives by aza-Wittig reaction using a thienyl carbodiimide
Hameed, Afaf M. Abdel
scheme or table, p. 411 - 414 (2012/06/01)
Azidation of aminothiophene derivative 1 afforded the corresponding azido derivative 2. The latter reacted with triphenylphosphine to afford iminophosphorane derivatives 3. Reacting 3 with phenylisocyanate gave the highly reactive carbodiimide intermediat
Development of scalable syntheses of selective PI3K inhibitors
Huang, Qinhua,Richardson, Paul F.,Sach, Neal W.,Zhu, Jinjiang,Liu, Kevin K.-C.,Smith, Graham L.,Bowles, Daniel M.
experimental part, p. 556 - 564 (2011/12/02)
On the basis of a more practical and scalable route to an iodothiophene, an efficient and reliable synthesis has been developed for three selective PI3K inhibitors. From this advanced intermediate, the three title compounds were each prepared in five additional steps. Key learnings also include: high throughput experimentation (HTE) screening toward a more robust Suzuki coupling, a more efficient triazole synthesis, and an acid/base cleanup developed to purify the final compounds. The final enabled synthesis required no column chromatography.
HETEROARYLS AND THEIR USE AS PI3K INHIBITORS
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Page/Page column 217-218, (2010/08/18)
This invention provides compounds of formula (IA) or (IB): wherein R1, R2, G1 and HY are as described in the specification. The compounds are inhibitors of PI3K and/or mTor and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.
THIOPHENE OR THIAZOLE DERIVATIVES AND THEIR USE AS PI3K INHIBITORS
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Page/Page column 44-45, (2010/01/12)
This invention provides compounds of formula (I) wherein R1, R2, CY, Y1, Y2, X1, X2, and X3 are as described in the specification. The compounds are inhibitors of PI3K and are th
