Search results for "Azoles"
showing 10 items of 899 documents
Entrectinib: a potent new TRK, ROS1, and ALK inhibitor
2015
Abstract: Introduction: Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC. Areas covered: This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-cl…
Structure-activity relationship studies of novel heteroretinoids: induction of apoptosis in the HL-60 cell line by a novel isoxazole-containing heter…
1999
In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were not active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, c…
Copper(II)-dipicolinate-mediated clickable azide–alkyne cycloaddition in water as solvent
2018
Copper(II)-dipicolinate complex [CuIIL(H2O)2] (1) (H2L = dipicolinic acid (H2dipic)) was synthesized via oxidation of copper(I) iodide and pyridine-2,6-dicarboxylic acid in water and acetonitrile in the presence of glycine. Complex 1 was characterized by FT-IR and elemental analysis and its structure confirmed by single crystal X-ray analysis. This complex is an efficient precatalyst that mediates azide-alkyne cycloaddition reactions in water at room temperature either in the absence or presence of a reducing agent. Compound 1-mediated azide-alkyne cycloaddition affords alkyl/aryl substituted 1,2,3-triazole heterocycles in a regioselective manner and excellent yields under very mild reactio…
Non-Classical Transformation of Benzendiazonium Hydrogen Sulfates. Access to 1,3-Dimethylisochromeno[4,3-c]pyrazol-5(1H)-one, a Potential Benzodiazep…
2013
The compound 2-((1,3-dimethyl-1H-pyrazol-5-yl)(methyl)carbamoyl)benzene-diazonium hydrogen sulfate (10) was reacted with copper sulfate and sodium chloride, in the presence of ascorbic acid as reducing agent, to afford a mixture of the chlorinated epimers 4′-chloro-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (18) and (19), the epimers 4′-hydroxy-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (20) and (21), and N-(1,3-dimethyl-1H-pyrazol-5-yl)benzamide (22). Under the foregoing conditions, diazonium salt 10 affords neither the 2-chloro-N-(1,3-dimethyl-1H-pyrazol-5-yl)-N-methylbenzamide (23) nor the tricyclic derivative 24, the classical products…
Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations
2014
AbstractThe eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment s…
Functional distinction between Cln1p and Cln2p cyclins in the control of the Saccharomyces cerevisiae mitotic cycle.
2004
Abstract Cln1p and Cln2p are considered as equivalent cyclins on the basis of sequence homology, regulation, and functional studies. Here we describe a functional distinction between the Cln1p and Cln2p cyclins in the control of the G1/S transition. Inactivation of CLN2, but not of CLN1, leads to a larger-than-normal cell size, whereas overexpression of CLN2, but not of CLN1, results in smaller-than-normal cells. Furthermore, mild ectopic expression of CLN2, but not of CLN1, suppresses the lethality of swi4swi6 and cdc28 mutant strains. In the absence of Cln1p, the kinetics of budding, initiation of DNA replication, and activation of the Start-transcription program are not affected; by cont…
4-(3H)-quinazolinones N-3 substituted with a five membered heterocycle: A promising scaffold towards bioactive molecules
2020
Abstract The quinazolinone nucleus represents, among the class of fused heterocycles, a very important scaffold to obtain molecules with biological activities. A review of literature revealed how such kind of fused heterocycles, coming from natural or synthetic source, are associated with a wide range of biological activities. This review is mainly directed towards the 4-(3H)-quinazolinones N-3 substituted with a five membered heterocycle in which all the possible combinations of nitrogen, sulfur and oxygen atoms are present.
Lack of antiandrogenic effects of topical bifonazole on sebaceous glands and hairs in the hamster flank organ.
1993
The activity of topically applied bifonazole was evaluated in vivo in the three androgen-dependent structures of the hamster flank organ, i.e. the pigmented spot, sebaceous glands and hairs. Topical bifonazole in our experience did not demonstrate any morphological effect on sebaceous gland and hair even when applied in the dosage of 3 mg/cm<sup>2</sup>/day. On the basis of our morphometric results we can conclude that topically applied bifonazole does not interfere with cutaneous androgen metabolic transformations in the pilosebaceous unit of the flank organ.
Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.
2004
OBJECTIVE Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. DESIGN Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzy…
ChemInform Abstract: Multiple 1,2,3-Thiadiazoles.
2010
A series of compounds 3a-d,i-n with two or three 1,2,3-thiadiazole rings, useful for photocrosslinking processes, was prepared from the di- or triketones 1a-d,i-n via the corresponding hydrazones 2a-d,i-n by applying the Hurd-Mori method. A special synthetic sequence, 1e, 2e, 3e, 3f/3g, was elaborated for the olefinic system 3h.