- Synthesis, SAR and docking studies of substituted aryl phenylthiazolyl phenylcarboxamide as potential protein tyrosine phosphatase 1B (PTP1B) inhibitors
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In our continued effort to discover novel PTP1B inhibitor with improved in vivo activity, we attempted to optimize our previously discovered lead compound by replacing the sulfonyl group with benzoyl group to yield compound II. Additional structural modif
- Varshney, Kanika,Gupta, Amit K.,Rawat, Arun,Srivastava, Rohit,Mishra, Akansha,Saxena, Mridula,Srivastava, Arvind K.,Jain, Sudha,Saxena, Anil K.
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p. 1378 - 1389
(2019/06/24)
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- Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
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A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl) -1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ~300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ~10-5.
- Meissner, Anja,Boshoff, Helena I.,Vasan, Mahalakshmi,Duckworth, Benjamin P.,Barry III, Clifton E.,Aldrich, Courtney C.
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p. 6385 - 6397
(2013/10/22)
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- Synthesis and biological evaluation of substituted 4-arylthiazol-2-amino derivatives as potent growth inhibitors of replicating Mycobacterium tuberculosis H37RV
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In search of potential therapeutics for tuberculosis, we describe herein synthesis and biological evaluation of some substituted 4-arylthiazol-2-amino derivatives as modified analogues of the antiprotozoal drug Nitazoxanide (NTZ), which has recently been reported as potent inhibitor of Mtb H37Rv (Mtb MIC = 52.12 μM) with an excellent ability to evade resistance. Among the synthesized derivatives, the two compounds 7a (MIC = 15.28 μM) and 7c (MIC = 17.03 μM) have exhibited about three times better Mtb growth inhibitory activity over NTZ and are free from any cytotoxicity (Vero CC50 of 244 and 300 μM respectively). These two compounds represent promising leads for further optimization.
- Roy, Kuldeep K.,Singh, Supriya,Sharma, Sandeep K.,Srivastava, Ranjana,Chaturvedi, Vinita,Saxena, Anil K.
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supporting information; experimental part
p. 5589 - 5593
(2011/10/12)
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- Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents
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A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, σ or μ) having high statistical significance > 99.9% (F2,22 > 15.0; F2,22α:0.001 = 11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.
- Saxena, Anil K.,Pandey, Suresh K.,Seth,Singh,Dikshit,Carpy
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p. 2025 - 2034
(2007/10/03)
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- STUDIES ON THE MOESSBAUER SPECTRA OF SOME IRON(III) COMPLEXES WITH IMIDES AS PRIMARY AND SOME N-ARYL-N'-BENZOYLTHIOCARBAMIDES AS SECONDARY LIGANDS. EFFECT OF AMBIENT TEMPERATURE
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Ten new mixed ligand complexes of iron(III) of the type , where Im = deprotonated phthalimide or succinimide and STC = some N-aryl-N'-benzoylthiocarbamide derivativesN-(2-chlorophenyl)-N'-benzoylthiocarbamide, N-(3-methoxyphenyl)-N'-be
- Mishra, Virendra
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p. 155 - 161
(2007/10/02)
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