- Investigation of the factors that dictate the preferred orientation of lexitropsins in the minor groove of DNA
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Lexitropsins are small molecules that bind to the minor groove of DNA as antiparallel dimers in a specific orientation. These molecules have shown therapeutic potential in the treatment of several diseases; however, the development of these molecules to target particular genes requires revealing the factors that dictate their preferred orientation in the minor grooves, which to date have not been investigated. In this study, a distinct structure (thzC) was carefully designed as an analog of a well-characterized lexitropsin (thzA) to reveal the factors that dictate the preferred binding orientation. Comparative evaluations of the biophysical and molecular modeling results of both compounds showed that the position of the dimethylaminopropyl group and the orientation of the amide links of the ligand with respect to the 5′-3′-ends; dictate the preferred orientation of lexitropsins in the minor grooves. These findings could be useful in the design of novel lexitropsins to selectively target specific genes.
- Alniss, Hasan Y.,Witzel, Ini-Isabeé,Semreen, Mohammad H.,Panda, Pritam Kumar,Mishra, Yogendra Kumar,Ahuja, Rajeev,Parkinson, John A.
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- Novel Thiazole Carboxylic Acid derivatives possessing a "zinc Binding Feature" as Potential human glyoxalase-I inhibitors
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Glyoxalase-I (Glo-I) enzyme is an attractive new target for developing new cancer therapeutics. This enzyme is a dimeric mononuclear zinc coordinating metalloenzyme, and the core zinc ion was utilized in designing potentially active inhibitors possessing
- Al-Balas, Qosay A.,Hassan, Mohammad A.,Jabal, Ghazi A. Al,Al-Shari, Nizar A.,Almaaytah, Ammar M.,El-Elimat, Tamam
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p. 1124 - 1134
(2017/11/14)
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- ACYLAMINOTHIAZOLE DERIVATIVES AND USE THEREOF AS BETA-AMYLOID INHIBITORS
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Compounds of formula (I) as defined herein: inhibit the formation of the β-amyloid peptide (β-A4) and are, therefore, useful in the treatment of pathologies in which a β-amyloid peptide (β-A4) formation inhibitor provides a therapeutic benefit. Particular
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Page/Page column 8
(2010/11/25)
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- Acylaminothiazole derivatives, preparation and therapeutic use thereof
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This invention discloses and claims a compound conforming to the general formula (I): Wherein R1, R2, R′2, R3, R4 and R5 are as described herein. The compounds of the present invention exhibit an inhibitory effect on the production of β-amyloid peptide (β-A4) by inhibition of gamma protease. Therefore, the compounds of the present invention are useful in the treatment of pathologies such as senile dementia, Alzheimer's disease, Down's syndrome, Parkinson's disease, amyloid angiopathy and/or cerebrovascular disorders.
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Page/Page column 6
(2008/06/13)
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- Identification of potent type I MetAP inhibitors by simple bioisosteric replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4-carboxylic acid thiazol-2-ylamide derivatives
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A series of thiazole-4-carboxylic acid thiazol-2-ylamide (TCAT, 4) derivatives were designed and synthesized according to simple bioisosteric replacement from previously reported pyridine-2-carboxylic acid thiazol-2-ylamide (PCAT) MetAP inhibitors. The preliminary SAR studies demonstrated that these TCAT series of compounds showed different activity and selectivity compared with those of the corresponding PCAT compounds. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.
- Cui, Yong-Mei,Huang, Qing-Qing,Xu, Jie,Chen, Ling-Ling,Li, Jing-Ya,Ye, Qi-Zhuang,Li, Jia,Nan, Fa-Jun
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p. 3732 - 3736
(2007/10/03)
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- Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity
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Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide an
- Khalaf, Abedawn I.,Waigh, Roger D.,Drummond, Allan J.,Pringle, Breffni,McGroarty, Ian,Skellern, Graham G.,Suckling, Colin J.
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p. 2133 - 2156
(2007/10/03)
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- Di-substituted aminomethyl-chroman derivative beta-3 adrenoreceptor agonists
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This invention is related to novel di-substituted aminomethyl chroman derivatives which are useful in the treatment of beta-3 receptor-mediated conditions.
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- Benzofuran and dihydrobenzofuran derivatives useful as beta-3 adrenoreceptor agonists
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This invention relates to novel benzofuran and dihydrobenzofuran compounds, pharmaceutical compositions containing such compounds, and methods of treating beta-3 adrenoreceptor-mediated conditions with such compositions.
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Page/Page column 35
(2010/01/31)
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- 2,6-Substituted chroman derivatives useful as beta-3 adrenoreceptor agonists
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This invention relates to novel 2,6-substituted chroman derivatives which are useful in the treatment of beta-3 adrenoreceptor-mediated conditions.
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- The Preparation of Thiazole-4- and -5-carboxylates, and an Infrared Study of their Rotational Isomers
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Convenient general procedures have been developed for preparing series of thiazole-4- and -5-carboxylates containing alkyl and halogeno substituents.While both series of esters show i.r. carbonyl doublets caused by rotational isomerism, the more intense absorptions of the 4-carboxylates are the lower wavenumber components, whereas those of the 5-carboxylates are the higher wavenumber components.In both series the stronger bands arise from the thermochemically more stable forms; identification of these forms as the carbonyl O,S-syn-s-trans rotamers is more certain with the 4-carboxylates than with the 5-carboxylates.
- Barton, Anne,Breukelman, Stephen P.,Kaye, Perry T.,Meakins, G. Denis,Morgan, David J.
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p. 159 - 164
(2007/10/02)
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