- An efficient synthesis, characterization and biological activity of novel Schiff bases of 2-aryl-1H-benzo[d]imidazole-4-carbohydrazide derivatives
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A series of N′-aryllidene-2-aryl-1H-benzo[d]imidazole-4-carbohydrazide (Schiff bases) 3a1-3d4 were synthesized by condensation reaction of 2-aryl-1H-benzo[d]imidazole-4-carbohydrazide (2a-2d) with substituted aromatic aldehyde. The c
- Gupta, Premlata,Jat, Kamal,Solanki, Vijendra Singh,Shrivastava, Ruchi
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p. 173 - 179
(2020/06/29)
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- FARNESOID X RECEPTOR AGONISTS
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The present invention relates to famesoid X receptors (FXR, NR1 H4) FXR is a member of the nuclear receptor class of ligand-activated transcription factors More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceu
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Page/Page column 126-127
(2009/01/23)
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- Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase
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The nuclear enzyme poly(ADP-ribose) polymerase (PARP) facilitates the repair of DNA strand breaks and is implicated in the resistance of cancer cells to certain DNA-damaging agents. Inhibitors of PARP have clinical potential as resistance-modifying agents capable of potentiating radiotherapy and the cytotoxicity of some forms of cancer chemotherapy. The preclinical development of 2-aryl-1H-benzimidazole-4-carboxamides as resistance-modifying agents in cancer chemotherapy is described. 1H-Benzimidazole-4-carboxamides, particularly 2-aryl derivatives, are identified as a class of potent PARP inhibitors. Derivatives of 2-phenyl-1H-benzimidazole-4-carboxamide (23, K(i) = 15 nM), in which the phenyl ring contains substituents, have been synthesized. Many of these derivatives exhibit K(i) values for PARP inhibition 10 nM, with 2-(4-hydroxymethylphenyl)-1H-benzimidazole-4-carboxamide (78, K(i) = 1.6 nM) being one of the most potent. Insight into structure-activity relationships (SAR) for 2-aryl-1H-benzimidazole-4-carboxamides has been enhanced by studying the complex formed between 2-(3-methoxyphenyl)-1H-benzimidazole-4-carboxamide (44, K(i) = 6 nM) and the catalytic domain of chicken PARP. Important hydrogen-bonding and hydrophobic interactions with the protein have been identified for this inhibitor. 2-(4-Hydroxyphenyl)-1H-benzimidazole-4-carboxamide (45, K(i) = 6 nM) potentiates the cytotoxicity of both temozolomide and topotecan against A2780 cells in vitro (by 2.8- and 2.9-fold, respectively).
- White,Almassy,Calvert,Curtin,Griffin,Hostomsky,Maegley,Newell,Srinivasan,Golding
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p. 4084 - 4097
(2007/10/03)
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