- Alkylsulfonamide-containing quinazoline derivatives as potent and orally bioavailable PI3Ks inhibitors
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Phosphoinositide 3-kinases (PI3Ks) are regarded as promising targets for treatment of various cancers due to their roles in regulating cell proliferation, differentiation, migration, and survival. Here we report our efforts to develop potent and orally bioavailable PI3K inhibitors for the treatment of cancers. The alkylsulfonamide-containing quinazoline derivatives A1–A18 significantly inhibited PI3Kα, and cell proliferation among HCT-116, MCF-7 and SU-DHL-6 cell lines. The optimal compound A1 displayed potent inhibitory activity against PI3Kα (IC50 = 4.5 nM), PI3Kβ (IC50 = 4.5 nM), PI3Kγ (IC50 = 4.5 nM), PI3Kδ (IC50 = 4.5 nM) and significantly inhibited the growth of HCT-116, MCF-7 and SU-DHL-6 cell lines with IC50 values of 0.82 μM, 0.99 μM and 0.19 μM, respectively. Western blot analysis demonstrated A1 significantly suppressed the phosphorylation of AKTS473 in a dose-dependent manner. Furthermore, A1 could markedly inhibit cancer growth at the dose of 25 mg/kg in nude mouse HCT-116 xenograft model in vivo without causing significant weight loss or toxicity.
- Hei, Yuan-Yuan,Zhang, San-Qi,Feng, Yifan,Wang, Jin,Duan, Weiming,Zhang, Hao,Mao, Shuai,Sun, Haopeng,Xin, Minhang
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- A mild method for the regioselective bromination of 2-aminopyridines
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An efficient and regioselective bromination of 2-aminopyridines was developed. The environmental friendly bromination occurs under mild and clean conditions using readily available 1-butylpyridinium bromide as the bromine source and hydrogen peroxide as the green oxidant.
- Xu, Tong,Zhou, Wen,Wang, Jing,Li, Xue,Guo, Jun-Wen,Wang, Bin
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supporting information
p. 5058 - 5061
(2015/01/08)
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- New tetracyclic 1,4-oxazepines constructed via practically simple tandem condensation strategy from readily available synthons
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A streamlined synthetic methodology towards novel tetracyclic 1,4-oxazepines from readily available precursors is described. The compounds, designed as more soluble version of the earlier described, poorly soluble dibenzo[b,f][1,4]oxazepines, were obtained in high yields and as a single regioisomer as a result of three tandem chemical events - nucleophilic aromatic substitution, Smiles rearrangement and denitrocyclization.
- Sapegin, Alexander V.,Kalinin, Stanislav A.,Smirnov, Alexey V.,Dorogov, Mikhail V.,Krasavin, Mikhail
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p. 1077 - 1083
(2014/01/23)
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- Controlling molecular tautomerism through supramolecular selectivity
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We have isolated the stable as well as the metastable tautomers of 1-deazapurine in the solid state by exploiting principles of supramolecular selectivity in the context of cocrystal design.
- Epa, Kanishka,Aakeroey, Christer B.,Desper, John,Rayat, Sundeep,Chandra, Kusum Lata,Cruz-Cabeza, Aurora J.
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supporting information
p. 7929 - 7931
(2013/09/02)
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- Synthesis and testing of new end-functionalized oligomers for molecular electronics
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Several new classes of oligomers have been synthesized with functionalities designed to aid in the understanding of molecular device behavior, specifically when molecules are interfaced between proximal electronic probes. The compounds synthesized are series of azobenzenes, bipyridines and oligo(phenylene vinylene)s that bear acetyl-protected thiols for ultimate attachment to metallic surfaces. Some initial electrochemical and solid-state test results are also reported.
- Flatt, Austen K.,Dirk, Shawn M.,Henderson, Jay C.,Shen, Dwanleen E.,Su, Jie,Reed, Mark A.,Tour, James M.
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p. 8555 - 8570
(2007/10/03)
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- ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE
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There are disclosed compounds of formula (I) STR1 and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.
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- Antagonists of gonadotropin releasing hormone
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There are disclosed compounds of formula (I) STR1 and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.
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- Heterocyclic compounds having anti-diabetic activity and their use
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Compounds of formula (I): STR1 [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.
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- Syntheses with Aromatic Nitramines. IX. Halogenation of 2- and 4-Nitraminopyridines
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Isomeric 2- and 4-nitraminopyridines (free acids and anions) were subjected to halogenation (iodination, bromination and chlorination).The iodination of nitraminopyridine anions failed, and the bromination and chlorination led selectively to 5-monohalogenated products independently of whether free acids or anions of nitraminopyridines were reacted.Key words: nitraminopyridines, halogenation
- Brzozka, L.,Baran, W.,Kraus, W.,Tomasik, P.
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p. 605 - 611
(2007/10/02)
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