Showing papers on "Pyrazole published in 2004"

A Highly Selective Catalytic Method for the Oxidative Functionalization of C−H Bonds

Abstract: This communication describes a new and highly practical Pd(II)-catalyzed method for the regio- and chemoselective oxidative functionalization of arenes and alkanes. Carbon−hydrogen bonds of substrates that contain a variety of directing groups (e.g., pyridine, azobenzene, pyrazole, and imine derivatives) are selectively transformed into esters, ethers, and aryl-halides under mild conditions. The scope of this reaction in terms of substrate, directing group, and oxidant is described, and a preliminary catalytic cycle is proposed.

Synthesis and Antibacterial Activity of a Novel Series of Potent DNA Gyrase Inhibitors. Pyrazole Derivatives

Abstract: We have previously found that a pyrazole derivative 1 possesses antibacterial activity and inhibitory activity against DNA gyrase and topoisomerase IV. Here, we synthesized new pyrazole derivatives and found that 5-[(E)-2-(5-chloroindol-3-yl)vinyl]pyrazole 16 possesses potent antibacterial activity and selective inhibitory activity against bacterial topoisomerases. Many of the synthesized pyrazole derivatives were potent against clinically isolated quinolone- or coumarin-resistant Gram-positive strains and had minimal inhibitory concentration values against these strains equivalent to those against susceptible strains.

Phosphodiesterase 4 inhibitors

Abstract: Selective PDE4 inhibition is achieved by aryl and heteroaryl pyrazole compounds. The compounds exhibit improved PDE4 inhibition as compared to compounds such as rolipram and show selectivity with regard to inhibition of other classes of PDEs.

Pyrazole derivatives as inhibitors of receptor tyrosyne kinases

Abstract: Disclosed is a compound of formula (I), wherein A is a direct bond, C is a carbocyclic or heterocyclic ring, R2 is C1-6alkyl, optionally substituted by one or more R10, R3 is fluoro and n is 1, R5 is H or C1-6alkyl optionally substituted by one or more R14, R6 and R7 may together form a 5 or 6 membered ring, and wherein the other substituents are as defined in the specification. Also disclosed is a process for preparing the compound, and the use of the compound for treating cancer, for inhibiting Trk activity, or for an anti-proliferative effect.

Synthesis of 4,5-diaryl-1H-pyrazole-3-ol derivatives as potential COX-2 inhibitors.

Abstract: 4,5-Diaryl-1H-pyrazole-3-ol was utilized as a versatile template to synthesize several classes of compounds such as pyrazolo-oxazines 7, pyrazolo-benzooxazines 9, pyrazolo-oxazoles 10, and its analogues 11a-c as potential COX-2 inhibitors. Compounds 11b,c were successfully synthesized with use of pyridinium p-toluenesulfonate mediated cyclization of the ketal intermediate. Diaryl-pyrazolo-benzooxazepine analogues were synthesized by using Cu-mediated cyclization of the O-alkylated arylbromide intermediate. Arylsulfonamides were synthesized efficiently on a large scale with 4-[4-(4-fluorophenyl)-5-hydroxy-2H-pyrazol-3-yl]benzenesulfonamide 31 template readily synthesized from commercially available 4-sulfamoyl benzoic acid 29. The structure of a representative compound from each class was confirmed by X-ray crystallography. Selected compounds tested for inhibitory activity against COX-1 and COX-2 enzymes showed good selectivity for COX-2 versus COX-1 enzyme.

Condensed ring compound

Abstract: A novel condensed ring compound having the activity of regulating GPR40-receptor function and being useful as an insulin secretion promoter or as a preventive/therapeutic agent for diabetes mellitus, etc. More specifically, a condensed ring compound of the formula: (I) [wherein: Ar is a substituted or unsubstituted cyclic group; ring A is a further substituted or unsubstituted ring (provided that the ring is none of thiazole, oxazole, imidazole and pyrazole); each of Xa and Xb independently is a bond or a spacer of 1 to 5 main chain atoms; Xc is O, S, SO or SO2; is or ; ring B is a 5 to 7-membered ring; Xd is a bond, CH or CH2; ...... is a single bond when Xd is a bond or CH2, and a double bond when Xd is CH; and R1 is a substituted or unsubstituted hydroxyl] or a salt thereof.

Antimicrobial activity of amino acid, imidazole, and sulfonamide derivatives of pyrazolo[3,4-d]pyrimidine

Abstract: Derivatives of pyrazolo[3,4-d]pyrimidine with amino acid 3a–d, imidazole 4a–d, carbonyl 6–9, pyrazole 10, pyrazolone 11, and sulfonamide 12–17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b,12, and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b,3c,12, and 16 were nearly as active as Terbinafine as positive control. © 2003 Wiley Periodicals, Inc. 15:57–62, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10212

Synthesis and Selective Cyclooxygenase-2 Inhibitory Activity of a Series of Novel, Nitric Oxide Donor-Containing Pyrazoles†

Abstract: The synthesis of a series of novel pyrazoles containing a nitrate (ONO2) moiety as a nitric oxide (NO)-donor functionality is reported Their COX-1 and COX-2 inhibitory activities in human whole blood are profiled Our data demonstrate that pyrazole ring substituents play an important role in COX-2 selective inhibition, such that a cycloalkyl pyrazole (6b) was found to be a potent and selective COX-2 inhibitor Other modifications at the 3 position of the central pyrazole ring (17b, 23b, 26b-I) enhanced COX-2 inhibitory potency Among the pyrazoles synthesized, the oxime (23b) was identified as the most potent COX-2 selective inhibitor Accordingly, 23b was profiled pharmacologically in the rat after oral administration and shown to possess potent antiinflammatory activity in the carrageenan-induced air-pouch model and less gastric toxicity than a standard COX-2 inhibitor when administered with background aspirin treatment We suggest that the enhanced gastric tolerance of an NO-donor COX-2 selective inhi

3,4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators

Abstract: The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. Formula (0). In formula (0): X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

Synthesis of pyrazole derivatives and their evaluation as photosynthetic electron transport inhibitors.

Abstract: Two series of new pyrazoles, namely six pyrazolo[1,5-a][1,3,5]triazine-2,4-dione and four pyrazolo[1,5-c][1,3,5]thiadiazine-2-one derivatives, were synthesized as potential inhibitors of the photosynthetic electron transport chain at the photosystem II level. The compounds were confirmed by 1H NMR, elemental, and IR analyses. Their biological activity was evaluated in vivo upon both the growth of blue-green algae and the photosynthetic oxygen evolution by eukaryotic algae and in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. Some compounds exhibited remarkable inhibitory properties, comparable to those of the reference commercial herbicides lenacil, diuron, and hexazinone. Results suggest that the substitution of triazine with thiadiazine ring may act as amplifier for herbicidal activity. Keywords: Herbicides; photosynthetic electron transport inhibitors; photosystem II

Ruthenium- and rhodium-catalyzed direct carbonylation of the ortho C-H bond in the benzene ring of N-arylpyrazoles.

Abstract: The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon monoxide and ethylene in the presence of Ru(3)(CO)(12) or Rh(4)(CO)(12) resulted in the site-selective carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones. A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher reactivities than would be expected, based on the pK(a) values of the conjugate acid of pyrazole. The choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best result.

Method for producing 2-dihaloacyl-3-amino-acrylic acid esters and 3-dihalomethyl-pyrazole-4-carboxylic acid esters

Abstract: The invention relates to a method for producing 2-dihaloacyl-3-amino-acrylic acid esters of formula (I). Said method is characterised in that acid halides of formula (II) are reacted with dialkyl amino-acrylic acid esters of formula (III), in which R, R1, R2, X1, X2 and Hal are defined as cited in the description, in a water-immiscible organic solvent in the presence of a base. The invention also relates to the novel 2-dihaloacyl-3-amino-acrylic acid esters of formula (I), to their use for producing 3-dihalomethyl-pyrazoles, to a method for producing 3-dihalomethyl-pyrazoles, in addition to novel 3-dihalomethyl-pyrazoles.

4,5-dihydro-1H-pyrazole derivatives with inhibitory nNOS activity in rat brain: synthesis and structure-activity relationships.

Abstract: In an attempt to find new compounds with neuroprotective activity, we have designed, synthesized and characterized 19 new nNOS inhibitors with a 4,5-dihydro-1H-pyrazole structure. Compounds 11r [1-cyclopropanecarbonyl-3-(2-amino-5-chlorophenyl)-4,5-dihydro-1H-pyrazole] and 11e [1-cyclopropanecarbonyl-3-(2-amino-5-methoxyphenyl)- 4,5-dihydro-1H-pyrazole] show the highest activities with inhibition percentages of 70% and 62%, respectively. A structure-activity relationship for the nNOS inhibition can be established from the structural comparison of these new pyrazole derivatives and the described synthetic kynurenines 10.

Pyrazole derivatives as cannabinoid receptor modulators

Abstract: The present application describes compounds according to Formula I, wherein A, B, E, R1, R2, R3, R4, Y and Z are described herein. Additionally, the present application describes pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents. Finally, the present application describes methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents.

Pyrazole derivatives as protein kinase modulators

Abstract: The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between Rl and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the inker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; Rl is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

5-membered heterocycle-based P38 kinase inhibitors

Abstract: Provided are 5-membered heterocycle-based p38 kinase inhibitors. Further provided are pyrazole and imidazole-based p38 kinase, including p38α and p38β kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of use of the compounds and compositions are also provided, including methods of treatment, prevention, or amelioration of one or more symptoms of p38 kinase mediated diseases and disorders, including, but not limited to, inflammatory diseases and disorders.