176752-73-1

Upstream product

• 45887-08-9 3-(1H pyrazol-3-yl)-pyridine 
• 77-78-1 dimethyl sulfate 
• 74-88-4 methyl iodide 
• 930-36-9 1-methyl-1H-pyrazole 
• 626-55-1 3-Bromopyridine 

Relevant academic research and scientific papers

Selective palladium-catalyzed direct C-H arylation of unsubstituted N-protected pyrazoles

A highly selective C-5 arylation of N-dimethylaminosulfamoyl-protected pyrazole with aryl bromides is catalyzed by 2-5 mol% palladium in the presence of triphenylphosphine ligand and carboxylic acid additive. Selectivities up to 45:1 (C-5:C-4) can be achieved by running the reaction in non-polar solvents. A thorough study of scope and limitations shows good general tolerance of aryl bromide substitution. However, limitations on tolerance of ortho-subsitution and protic functional groups were established. Together with a telescoped deprotection step this method presents a viable alternative for the synthesis of C-3 arylated pyrazole building blocks.

Synthesis of 1-methyl-5-(pyrazol-3- and -5-yl- and 1,2,4-triazol-3- and 5-yl)-1,2,3,6-tetrahydropyridine derivatives and their evaluation as muscarinic receptor ligands

A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1,2,4-triazol-3- and 5-yl)-1,2,3,6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M1, M2, and M3 muscarinic receptors using [3H]pirenzepine and [3H]NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 51 and 6 i displayed good M1 and M3 antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.

Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives

A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of 3H-OXO-M and 3H-PZ. Preferential inhibition of 3H-OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. All compounds with agonistic properties showed 3H-PZ/3H-OXO-M potency ratios in excess of 20. In contrast, for antagonists this ratio was found to be close to unity. Mono-halogenation resulted in compounds (4b and 4d) with M3 agonistic properties as shown by their atropine sensitive stimulant properties in the guinea pig ileum, but with very little or no M1 activity. Some minor in vivo effects were observed for both these compounds, with the iodinated compound 4d inducing salivation. Compound 4d also showed some positive mnemonic properties in rats where spatial short-term memory had been compromised by temporary cholinergic depletion. These data indicate that some M3 agonism may be desired in therapeutic agents aimed at the treatment of the cognitive deficits of Alzheimer's disease patients.