5250-25-9Relevant academic research and scientific papers
Tetrazolylhydrazides as selective fragment-like inhibitors of the JumonjiC-domain-containing histone demethylase KDM4A
Rüger, Nicole,Roatsch, Martin,Emmrich, Thomas,Franz, Henriette,Schüle, Roland,Jung, Manfred,Link, Andreas
supporting information, p. 1875 - 1883 (2015/11/10)
The JumonjiC-domain-containing histone demethylase 2A (JMJD2A, KDM4A) is a key player in the epigenetic regulation of gene expression. Previous publications have shown that both elevated and lowered enzyme levels are associated with certain types of cancer, and therefore the definite role of KDM4A in oncogenesis remains elusive. To identify a novel molecular starting point with favorable physicochemical properties for the investigation of the physiological role of KDM4A, we screened a number of molecules bearing an iron-chelating moiety by using two independent assays. In this way, we were able to identify 2-(1H-tetrazol-5-yl)acetohydrazide as a novel fragment-like lead structure with low relative molecular mass (Mr=142 Da), low complexity, and an IC50 value of 46.6 μm in a formaldehyde dehydrogenase (FDH)-coupled assay and 2.4 μm in an antibody-based assay. Despite its small size, relative selectivity against two other demethylases could be demonstrated for this compound. This is the first example of a tetrazole group as a warhead in JMJD demethylases. Anchor fragment: To develop non-promiscuous metalloenzyme inhibitors, a metal-complexing acetohydrazide group was integrated in a tetrazolyl fragment, which can be matured into a scaffold to promote further selectivity at the ligand backbone binding site of these emerging drug targets.
Substituted enaminones, their derivatives and uses thereof
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Page/Page column 18, (2010/11/25)
The present invention is related substituted enaminones represented by a compound of Formula I that are novel allosteric modulators of α7 nAChRs. The invention also discloses the treatment of disorders that are responsive to enhancement of acetylcholine a
A reagent, ethyl 2-(2-tert-butyl-2H-tetrazol-5-yl)-3-(dimethylamino)acrylate (DMTE), for facile synthesis of 2,3-(ring fused)-5-(5-tetrazolyl)-4H-pyrimidin-4-one derivatives
Kanno,Yamaguchi,Ichikawa,Isoda
, p. 1099 - 1105 (2007/10/02)
A method for synthesizing 2,3-(ring fused)-5-(5-tetrazolyl)-4H-pyrimidin-4-one derivatives from ethyl 2-(2-tert-butyl-2H-tetrazol-5-yl)-3-(dimethylamino)acrylate (DMTE) (4a) and amino-heterocycles is described. The structure of DMTE, which was prepared from ethyl (2-tert-butyl-2H-tetrazol-5-yl)acetate (3a) with dimethylformamide diethylacetal, was determined by X-ray analysis to be Z form. The reaction of 2-amino-5-methyloxazole (6) with DMTE in acetic acid gave the oxazolo[3,2-a]pyrimidine derivative (8), heating of which in concentrated sulfuric acid afforded the desired tetrazole derivative (20). Pyrimido[2,1-b]benzothiazole (21), pyrazolo[1,5-a]pyrimidine (22 and 23) and [1,2,4]triazolo[1,5-a]pyrimidine (24) derivatives were prepared in a similar manner.
Synthesis, biological profile, and quantitative structure - Activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
Sit,Parker,Motoc,Han,Balasubramanian,Catt,Brown,Harte,Thompson,Wright
, p. 2982 - 2999 (2007/10/02)
A series of 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(alkyltetrazol-5-yl)-6,8-nonad ienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having 1N-methyltetrazol-5-yl attached to the C8-position (3a, 4a, R1 = R2 = F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the IC50 for the chiral form of 3a is 19 nM, K(i) = 4.3 x 10-9 M when K(m) for HMG-CoA is 28 x 10-6 M; the ED50 (oral) value corresponding to the lactone derivative (4a, BMY 22089) is approximately 0.1 mg/kg. Further, BMY 21950 is nearly 2 orders of magnitude more active in parenchymal hepatocytes, from which most of the serum cholesterol originates, than in other cell preparations (such as spleen, testes, ileum, adrenal, and ocular lens epithelial cells; Table III). This apparent tissue specificity may be highly beneficial since the blocking of cholesterol biosynthesis in other vital organs could eventually lead to undesirable side effects. In addition to the chemical synthesis and biological evaluation, a theoretical study aimed at relating the HMG-CoA reductase inhibitory potency to the three-dimensional structure of the inhibitors was undertaken. With a combination of molecular mapping and 3D-QSAR techniques, it was possible to determine a logical candidate for the conformation of the bound inhibitor and to quantitatively relate inhibitory potency to the shape and size of both the binding site and the C8-substituent.
Antihypercholesterolemic tetrazole compounds
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, (2008/06/13)
Compounds of the formula STR1 wherein R1 and R4 each are independently hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy, or trifluoromethyl; R2, R3, R5 and R6 each are independently hydrogen, halogen C1-4 alkyl or C1-4 alkoxy; tet is STR2 n is an integer of from 0 to 2, inclusive; A is STR3 R7 is hydrogen, C1-4 alkyl, C1-4 alkoxy(lower) alkyl or (2-methoxyethoxy)methyl; X is --OH or =O; and R8 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt, are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.
Intermediates for the preparation of antihypercholesterolemic tetrazole compounds
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, (2008/06/13)
This invention provides novel tetrazole intermediates of the formula STR1 wherein R1 and R4 each are independently hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy or trifluoromethyl; R2,R3,Rsup
