- Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives
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Ten new dabigatran derivatives (7a–j) with high docking scoring were designed, synthesised and biologically evaluated. The inhibitory in vitro activity of these compounds on thrombin was evaluated on the basis of preliminary activity screening results. The IC50 values of compounds 7a, 7d and 7j were 1.92, 2.17 and 1.54 nM, respectively, and are equivalent to the dabigatran (IC50 = 1.20 nM). Therefore, the most active compound, 7j, was selected to further investigate the anticoagulant activity in rats. Compound 7j presented excellent in vivo inhibitory effects on arteriovenous thrombosis, and the inhibition rate was (84.19 ± 1.14) %. The anticoagulant activity of compound 7k synthesised in the previous work was evaluated in vivo, and its inhibition rate was (85.58 ± 2.89) %. This rate was nearly equivalent to that of dabigatran (85.07 ± 0.61) %. Results indicated that compounds 7a, 7d, 7j and 7k can be further studied as novel antithrombin drug candidates.
- Liu, Qianqian,Ren, Yujie,Zhang, Tianrong
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- Synthesis and Catalytic Application of Mixed Valence Iron (FeII/FeIII)-Based OMS-MIL-100(Fe) as an Efficient Green Catalyst for the aza-Michael Reaction
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Abstract: In the present study, open metal site iron-based MOF [MIL-100(Fe)], by a solvothermal method with polygonal morphology, are synthesised and then applied as a heterogeneous green catalyst for aza-Michael addition of various amines with α, β-unsaturated compounds. The MIL-100(Fe) was found to be efficient, selective, green and heterogeneous catalyst for the aza-Michael reaction. The proposed catalyst has better recyclability and can be reused six times without apparent loss of activity. Graphical Abstract: [Figure not available: see fulltext.].
- Rostamnia, Sadegh,Alamgholiloo, Hassan
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p. 2918 - 2928
(2018/07/30)
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- Synthesis and biological evaluation of some new 2,5-Substituted 1-Ethyl-1H-benzoimidazole fluorinated derivatives as direct thrombin Inhibitors
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A new series of fluorinated 2,5-substituted 1-ethyl-1H-benzimidazole derivatives were synthesized from starting compounds 3a-i, which were prepared from acrylic acid ethyl ester and the appropriate amines using trifluoromethanesulfonic acid as a catalyst. A total of 9 novel derivatives were synthesized through 9 steps. All of them were evaluated for thrombin inhibition activity in vitro for the first time. We have altered their structures using different substituents on the amines to assess their structure-activity relationships as direct thrombin inhibitors. All the compounds were effective thrombin inhibitors, with IC50 values ranging from 3.39 to 23.30nM. Among the compounds synthesized, compounds 14a, 14b, 14d, 14e, and 14h exhibited greater anticoagulant activity than argatroban (IC50=9.36nM). Furthermore, compound 14h synthesized starting with 2-amino-pyridine was the most potent thrombin inhibitor with an IC50 value of 3.39nM. Molecular modeling studies were performed to determine the probable interactions of the most potent compounds 14a, 14e, and 14h with their protein receptor (PDB ID: 1KTS). Docking data show that the active compounds inhibit thrombin in a similar mode to that of the potent anticoagulant dabigatran. A new series of fluorinated derivatives were evaluated for their in vitro thrombin inhibition activities. 3-({2-[(4-Carbamimidoyl-2-fluoro-phenylamino)-methyl]-1-ethyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid 14h shows the most potent antithrombin activity (IC50=3.39nM). Molecular docking revealed that its inhibition mode was similar to that of dabigatran.
- Li, Meilin,Ren, Yujie
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p. 353 - 365
(2015/05/13)
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- Synthesis of new tetracyclic 7-oxo-pyrido[3,2,1-de]acridine derivatives
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A series of (±)3-hydroxyl- and 2,3-dihydroxy-2,3-dihydro-7- oxopyrido[3,2,1-de]acridines were synthesized for antitumor evaluation. These agents can be considered as analogues of glyfoline or (±)1,2- dihydroxyacronycine derivatives. The key intermediates,
- Chen, Ching-Huang,Lin, Yi-Wen,Kakadiya, Rajesh,Kumar, Amit,Chen, Yu-Ting,Lee, Te-Chang,Su, Tsann-Long
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experimental part
p. 5883 - 5893
(2011/09/12)
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- Cerium(IV) ammonium nitrate (CAN) catalyzed aza-Michael addition of amines to α,β-unsaturated electrophiles
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Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic amines with α,β-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.
- Duan, Zheng,Xuan, Xuejie,Li, Ting,Yang, Chenfei,Wu, Yangjie
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p. 5433 - 5436
(2007/10/03)
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- 6,7-dihydropyrrol[3,4-c]pyrido[2,3-d]pyrimidine derivatives
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The present invention concerns compounds of the formula: STR1 wherein R is a lower alkyl group, an aryl group or an alkylaryl group and X and Y are the same or different, and each is OH, NH2, or SH. The aryl group or the aryl moiety of the alkylaryl group may be unsubstituted, monosubstituted, disubstituted or trisubstituted. If substituted, each substituent may independently be an alkyl group, an alkyloxy group or a halogen. The present invention also provides methods for synthesizing the compounds described above.
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- Studies in Antifertility Agents: Part XXVII - Synthesis of 2-Acetyl-3-aryl-5-tosyl-7/8-H (or methoxy)-3,3a,4,5-tetrahydropyrazoloquinolines
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N-Tosyl-2,3-dihydro-4-quinolones (12-14), prepared from aniline, m- and p-anisidines by reported procedures, on condensation with araldehydes in the presence of NaOMe give the corresponding 3-arylidene-4-quinolones (15-18).Refluxing of 15-18 with NH2-NH2*H2O in gl.AcOH affords the title compounds, 2-acetyl-3-aryl-5-tosyl-7/8-H (or methoxy)-3,3a,4,5-tetrahydropyrazoloquinolines (19-22).The stereochemistry of the title compounds based on the assignments of C3-H, C3a-H, C4-H2 protons has been studied by PMR decoupling experiments.In preliminary screening, compounds 19 and 22 have been found to prevent pregnancy at 20 mg/kg dose in female albino rats, but are ineffective at lower doses.None of the compounds tested shows any significant pharmacological activity.
- Kelkar, Prabhakar M.,Sangwan, Naresh K.,Rastogi, Shri Nivas,Anand, Nitya
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p. 297 - 300
(2007/10/02)
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- Formation of 2,3-Dihydro-4(1H)-quinolones and Related Compounds via Fries-type Acid-catalysed Rearrangement of 1-Arylazetidin-2-ones
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A variety of 1-arylazetidin-2-ones were treated with trifluoroacetic acid under reflux, methanesulphonic acid at 100 deg C, or conc. sulphuric acid to give the corresponding 2,3-dihydro-4(1H)-quinolones via acyl migration and N-CO fission.In the case of 1-(3-substituted phenyl)azetidin-2-ones, two positional isomeric products, 5- and 7-substituted 2,3-dihydro-4(1H)-quinolones were obtained. 4-Methyl, 4-ethoxycarbonyl, and 4-piperidin-2-yl-1-arylazetidin-2-ones and their analogues were also converted into the corresponding 2-substituted 2,3-dihydro-4(1H)-quinolones under acidic conditions.The 3-substituted 1-phenylazetidin-2-ones (36) and (37) were converted into the furoquinoline systems (38) and (40), respectively, by application of this method.
- Kano, Shinzo,Ebata, Tsutomu,Shibuya, Shiroshi
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p. 2105 - 2111
(2007/10/02)
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