3012-80-4Relevant articles and documents
Cobalt(II) and nickel(II) complexes with 1-methyl-2-pyridin-2-yl-1H- and 1-methyl-2-phenyliminomethyl-1H-benzimidazoles and the closo-decaborate anion
Avdeeva,Polyakova,Goeva,Malinina,Zhdanov,Zhizhin, K. Yu.,Kuznetsov
, p. 817 - 822 (2015)
Synthesis of cobalt(II) and nickel(II) complexes with the closo-decaborate anion and benzimidazole derivatives (L1 = C13N3H11, L2 = C15N3H13) of the general formula [ML3][B10H10] (M = Co, Ni) is described. Complexes have been characterized by elemental analysis, IR and UV spectroscopy. The structure of a [Ni(L1)3][B10H10] · 1.797CH3CN single crystal has been determined by X-ray diffraction. The imidazole and pyridine N atoms of three L1 molecules, two of which are disordered, form the distorted octahedral environment of the Ni atom. In the crystal, the majority of complexes [Ni(L1)3]2+ have the meridional configuration. The Ni-N bonds with the imidazole nitrogen atoms (2.010(4)-2.076(3) ?) are shorter than those with the pyridine atoms (2.132(4)-2.179(5) ?). This nonequivalence of the Ni-N bonds is responsible for the low magnetic susceptibility of the compound.
Kallikrein 5 inhibitors identified through structure based drug design in search for a treatment for Netherton Syndrome
White, Gemma V.,Edgar, Emma V.,Holmes, Duncan S.,Lewell, Xiao Qing,Liddle, John,Polyakova, Oxana,Smith, Kathrine J.,Thorpe, James H.,Walker, Ann L.,Wang, Yichen,Young, Robert J.,Hovnanian, Alain
, p. 821 - 825 (2019)
Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10–100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology.
Metal-free oxidative decarbonylative halogenation of fused imidazoles
Kumar, Gulshan,Shankar, Ravi,Singh, Davinder,Tali, Javeed Ahmad
, p. 20551 - 20555 (2021/11/23)
An efficient strategy has been developed for the deformylative halogenation of carbaldehyde imidazo-fused heterocycles in the presence of TBHP controlled by temperature. A convenient and sequential functionalization (C8 to C3) portrays the synthetic utility of the current method.N-Heterocycle benzamide products were also observedviathe ring opening of imidazopyridines through the cleavage of C-C bond at high temperatures. Features of this method include temperature-controlled excellent regioselectivity, mild conditions and functional group tolerance.
Efficient synthesis of acrylates bearing an aryl or heteroaryl moiety: One-pot method from aromatics and heteroaromatics using formylation and the horner-wadsworth-emmons reaction
Yasukata, Tatsuro,Matsuura, Takaharu
, p. 527 - 533 (2021/03/22)
Acrylates bearing an aryl or heteroaryl moiety were efficiently prepared by a one-pot process employing a sequence of lithiation, formylation and the Horner-Wadsworth-Emmons reaction starting from aromatic and heteroaromatic compounds. This method can efficiently introduce an acrylate moiety into aromatic and heteroaromatic compounds.
Reactions of 2-carbonyl- And 2-hydroxy(or methoxy)alkylsubstituted benzimidazoles with arenes in the superacid CF3SO3H. NMR and DFT studies of dicationic electrophilic species
Ryabukhin, Dmitry S.,Turdakov, Alexey N.,Soldatova, Natalia S.,Kompanets, Mikhail O.,Ivanov, Alexander Yu.,Boyarskaya, Irina A.,Vasilyev, Aleksander V.
supporting information, p. 1962 - 1973 (2019/09/03)
Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkylbenzimidazoles with arenes in the Br?nsted superacid TfOH resulted in the formation of the corresponding Friedel-Crafts reaction products, 2-diarylmethyl and 2-arylmethyl-substituted benzimidazoles, in yields up to 90%. The reaction intermediates, protonated species derived from starting benzimidazoles in TfOH, were thoroughly studied by means of NMR and DFT calculations and plausible reaction mechanisms are discussed.
Photoredox-Catalyzed Decarboxylative C-H Acylation of Heteroarenes
Jia, Wei,Jian, Yong,Huang, Binbin,Yang, Chao,Xia, Wujiong
supporting information, p. 1881 - 1886 (2018/08/28)
A mild, environmentally friendly, and regioselective acylation of heterocycles with inexpensive carboxylic acids is reported via photoredox catalysis. The strategy is highlighted with good functional group tolerance and substrate scope which could rapidly
Quinolinones as Inhibitors of Translation Initiation Complex
-
Paragraph 0597, (2018/03/25)
Provided herein are compounds and pharmaceutical compositions comprising quinolinones. The quinolinones and compositions thereof are useful as eukaryotic translation initiation factor 4F (eIF4F) complex modulators.
New (E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies
Sharma, Pankaj,Thummuri, Dinesh,Reddy, T. Srinivasa,Senwar, Kishna Ram,Naidu,Srinivasulu, Gannoju,Bharghava, Suresh K.,Shankaraiah, Nagula
, p. 584 - 600 (2016/07/22)
A new series of (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-one derivatives has been synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines of prostate (PC-3 and DU-145) and breast (BT-549, MDA-MB-231, MCF-7, 4T1), non-small lung (A549) and gastric (HGC) cancer cells along with normal breast epithelial cells (MCF10A). Among the tested compounds, 8l showed significant cytotoxic activity against MDA-MB-231 and 4T1 cancer cells with IC50values of 3.26 ± 0.24 μM and 5.96 ± 0.67 μM respectively. The compounds 8f, 8i, 8l and 8o were also screened on normal human breast epithelial cells (MCF10A) and found to be safer with lesser cytotoxicity. The treatment of MDA-MB-231 cells with 8l led to inhibition of cell migration ability through disruption of F-actin protein assembly. The flow-cytometry analysis reveals that the cells arrested in G0/G1 phase of the cell cycle. Further, the compound 8l induced apoptosis of MDA-MB-231 cells was characterized by different staining techniques such as Acridine Orange/Ethidium Bromide (AO/EB), DAPI, annexin V-FITC/PI, Rhodamine-123 and MitoSOX red assay. Western blot studies demonstrated that the compound 8l treatment led to activation of caspase-3, increased expression of cleaved PARP, increased expression of pro-apoptotic Bax and decreased expression of anti-apoptotic Bcl-2 in MDA-MB-231 cancer cells.
Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents
Sharma, Pankaj,Srinivasa Reddy,Thummuri, Dinesh,Senwar, Kishna Ram,Praveen Kumar, Niggula,Naidu,Bhargava, Suresh K.,Shankaraiah, Nagula
, p. 608 - 621 (2016/09/14)
A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50value of 11.46?±?1.46?μM on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549?cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p.
Synthesis and biological evaluation of heterocyclic privileged medicinal structures containing (benz)imidazole unit
Boulebd, Houssem,Zama, Sana,Insaf, Bataiche,Bouraiou, Abdelmalek,Bouacida, Sofiane,Merazig, Hocine,Romero, Alejandro,Chioua, Mourad,Marco-Contelles, José,Belfaitah, Ali
, p. 2209 - 2220 (2016/11/17)
Abstract: New heterocyclic privileged medicinal scaffolds involving 4H-pyran, 1,4-dihydropyridine, quinazoline, and 2-aminochromene bearing a (benz)imidazole unit were prepared in good to excellent yields, and evaluated for their in vitro hepatotoxicity on HepG2 cells and antioxidant activity using DPPH radical-scavenging assay. From these results, 2-amino-4-(1-methyl-1H-imidazol-2-yl)-4H-benzo[h]chromene-3-carbonitrile has been identified as a racemic, readily available imidazole derivative, significantly less hepatotoxic than tacrine at 100?μM concentration. One compound was found to be a potent antioxidant agent. The catalytic effect of the 1-methylimidazole unit, in the synthesis of some heterocycle, was also demonstrated. Crystal X-ray structures are reported for six compounds. Graphical abstract: [Figure not available: see fulltext.]
