Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Construction of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines by ring closure of 3-acylpyridine N-oxide tosylhydrazones.

ABSTRACT: 3-Acylpyridine N-oxide tosylhydrazones give good overall yields of a mixture of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines when treated with an electrophilic additive and an amine base. (Z)-Hydrazones cyclize readily, while (E)-hydrazones fail to react under the reported conditions. The reaction takes place at room temperature, and moderate regiocontrol over the cyclization can be achieved by varying the electrophile/solvent combination.

SUBMITTER: Lominac WJ

PROVIDER: S-EPMC3278155 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Construction of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines by ring closure of 3-acylpyridine N-oxide tosylhydrazones.

Lominac William J WJ D'Angelo Megan L ML Smith Mark D MD Ollison Darius A DA Hanna James M JM

Tetrahedron letters 20120201 8

3-Acylpyridine N-oxide tosylhydrazones give good overall yields of a mixture of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines when treated with an electrophilic additive and an amine base. (Z)-Hydrazones cyclize readily, while (E)-hydrazones fail to react under the reported conditions. The reaction takes place at room temperature, and moderate regiocontrol over the cyclization can be achieved by varying the electrophile/solvent combination. ...[more]

PMID: 22345825

Similar Datasets

Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines.

Project description:A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

| S-EPMC8588486 | biostudies-literature

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines - sequential versus multicomponent reaction approach.

Project description:A straightforward synthesis of 6-substituted 1-phenyl-3-trifluoromethyl-1H-pyrazolo[4,3-c]pyridines and the corresponding 5-oxides is presented. Hence, microwave-assisted treatment of 5-chloro-1-phenyl-3-trifluoromethylpyrazole-4-carbaldehyde with various terminal alkynes in the presence of tert-butylamine under Sonogashira-type cross-coupling conditions affords the former title compounds in a one-pot multicomponent procedure. Oximes derived from (intermediate) 5-alkynyl-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehydes were transformed into the corresponding 1H-pyrazolo[4,3-c]pyridine 5-oxides by silver triflate-catalyzed cyclization. Detailed NMR spectroscopic investigations ((1)H, (13)C, (15)N and (19)F) were undertaken with all obtained products.

| S-EPMC4142841 | biostudies-literature

Synthesis and vectorial functionalisation of pyrazolo[3,4-<i>c</i>]pyridines.

Project description:Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target protein. Here we describe the synthesis of 5-halo-1H-pyrazolo[3,4-c]pyridine scaffolds and demonstrate how these compounds can be selectively elaborated along multiple growth-vectors. Specifically, N-1 and N-2 are accessed through protection-group and N-alkylation reactions; C-3 through tandem borylation and Suzuki-Miyaura cross-coupling reactions; C-5 through Pd-catalysed Buchwald-Hartwig amination; and C-7 through selective metalation with TMPMgCl.LiCl followed by reaction with electrophiles or transmetalation to ZnCl2 and Negishi cross-coupling. Linking multiple functionalisation strategies emulates a hit-to-lead pathway and demonstrates the utility of pyrazolo[3,4-c]pyridines to FBDD.

| S-EPMC10667592 | biostudies-literature

Straightforward and Efficient Protocol for the Synthesis of Pyrazolo [4,3-<i>b</i>]pyridines and Indazoles.

Project description:An efficient method for the synthesis of pyrazolo [4,3-b]pyridines has been developed on the basis of readily available 2-chloro-3-nitropyridines via a sequence of SNAr and modified Japp-Klingemann reactions. The method offers a number of advantages including utilization of stable arenediazonium tosylates, operational simplicity as well as combining the azo-coupling, deacylation and pyrazole ring annulation steps in a one-pot manner. An unusual rearrangement (C-N-migration of the acetyl group) was observed and a plausible mechanism was proposed based on the isolated intermediates and NMR experiments. In addition, the developed protocol was successfully applied to the synthesis of 1-arylindazoles combining the Japp-Klingemann reaction and cyclization of the resulting hydrazone as a one-pot procedure.

| S-EPMC9860909 | biostudies-literature

Organometallic 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines as potential anticancer agents.

Project description:Six organometallic complexes of the general formula [M(II)Cl(?(6)-p-cymene)(L)]Cl, where M = Ru (11a, 12a, 13a) or Os (11b, 12b, 13b) and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) have been synthesized. The latter are known as potential cyclin-dependent kinase (Cdk) inhibitors. All compounds have been comprehensively characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, UV-vis spectroscopy, ESI mass spectrometry, and X-ray crystallography (11b and 12b). The multistep synthesis of 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3), which was reported by other researchers, has been modified by us essentially (e.g., the synthesis of 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (3) via 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine (2); the synthesis of 1-methoxymethyl-2,3-diaminobenzene (5) by avoiding the use of unstable 2,3-diaminobenzyl alcohol; and the activation of 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acids (1, 3) through the use of an inexpensive coupling reagent, N,N'-carbonyldiimidazole (CDI)). Stabilization of the 7b tautomer of methoxymethyl-substituted L3 by coordination to a metal(II) center, as well as the NMR spectroscopic characterization of two tautomers 7b-L3 and 4b'-L3 in a metal-free state are described. Structure-activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells, as well as Cdk inhibitory activity, are also reported.

| S-EPMC3255473 | biostudies-literature

Isoprop-yl (3,4-dimethyl-5,5-dioxo-4H-pyrazolo-[4,3-c][1,2]benzothia-zin-2-yl)acetate.

Project description:In the title mol-ecule, C(16)H(19)N(3)O(4)S, the heterocyclic thia-zine ring adopts a half-chair conformation, with the S and N atoms displaced by 0.547?(2) and -0.254?(3)?Å, respectively, from the plane formed by the remaining atoms. In the crystal, weak C-H?N and C-H?O hydrogen bonds link the mol-ecules.

| S-EPMC2983407 | biostudies-literature

Four-component strategy for selective synthesis of azepino[5,4,3-cd]indoles and pyrazolo[3,4-b]pyridines.

Project description:A novel four-component strategy for the selective synthesis of fused azepino[5,4,3-cd]indoles and pyrazolo [3,4-b]pyridines has been established. The bond-forming efficiency, accessibility of starting materials and substrate scope provide invaluable access to tetra-, and bis-heterocyclic scaffolds.

| S-EPMC4060249 | biostudies-literature

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo-[4,3-c][1,2]benzothia-zin-2-yl)acetic acid.

Project description:In the title mol-ecule, C(13)H(13)N(3)O(4)S, the heterocyclic thia-zine ring adopts a half-chair conformation in which the S and an adjacent C atom are displaced by 0.919?(3) and 0.300?(4)?Å, respectively, on the same side of the mean plane formed by the remaining ring atoms. The mean planes of the benzene and pyrazole rings are inclined at a dihedral angle of 18.32?(12)° with respect to each other. The acetate group is oriented at 80.75?(8)° with respect to the pyrazole ring. The crystal structure is stabilized by O-H?N and C-H?O hydrogen bonds, resulting in fused eight- and seven-membered rings with R(2) (2)(8) and R(2) (2)(7) graph-set motifs, respectively.

| S-EPMC3379518 | biostudies-literature

3,4-Dimethyl-2-(2-oxo-2-phenyl-eth-yl)-2H,4H-pyrazolo-[4,3-c][1,2]benzothia-zine-5,5-dione.

Project description:In the title mol-ecule, C(19)H(17)N(3)O(3)S, the heterocyclic thia-zine ring adopts a half-chair conformation with the S and N atoms displaced by 0.530?(5) and 0.229?(6)?Å, respectively, on opposite sides of the mean plane formed by the remaining ring atoms. The ethanone group lies at an angle of 3.8?(3)° with respect to the benzene ring, which lies almost perendicular to the pyrazole ring, with a dihedral between the two planes of 89.22?(11)°. Weak inter-molecular C-H?O hydrogen-bonding inter-actions are present.

| S-EPMC3275247 | biostudies-literature

Ethyl 2-(3,4-dimethyl-5,5-dioxo-1H,4H-benzo[e]pyrazolo-[4,3-c][1,2]thia-zin-1-yl)acetate.

Project description:In the title mol-ecule, C(15)H(17)N(3)O(4)S, the heterocyclic thia-zine ring adopts a twist-boat conformation, which differs from that in related compounds, with adjacent S and C atoms displaced by 0.981?(4) and 0.413?(5)?Å, respectively, on the same side of the mean plane formed by the remaining ring atoms. The mean plane of the benzene ring makes a dihedral angle of 23.43?(14)° with the mean plane of the pyrazole ring. In the crystal, mol-ecules are connected by weak C-H?O hydrogen bonds to form a three-dimensional network. The H atoms of the methyl group attached to the pyrazole ring were refined over six sites with equal occupancies.

| S-EPMC3470368 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data