1904-31-0Relevant academic research and scientific papers
Synthesis of vicinal aminoiodo- and (acetylamino)iodo-1-alkylpyrazoles
Tret'yakov,Vasilevsky
, p. 2585 - 2587 (1996)
3- and 5-(Acetylamino)-4-iodo-1-alkylpyrazoles were obtained by successive acylation and iodination from 3- and 5-amino-1-alkylpyrazoles without isolating intermediate (acetylamino)pyrazoles. 3- and 5-Iodo- and 3,5-diiodo-4-amino-1-methylpyrazoles were synthesized from appropriate iodonitropyrazoles by reduction with SnCl2 in HCl.
Design and synthesis of highly potent and isoform selective JNK3 inhibitors: SAR studies on aminopyrazole derivatives
Zheng, Ke,Iqbal, Sarah,Hernandez, Pamela,Park, Hajeung,Lograsso, Philip V.,Feng, Yangbo
supporting information, p. 10013 - 10030 (2015/02/19)
The c-jun N-terminal kinase 3 (JNK3) is expressed primarily in the brain. Numerous reports have shown that inhibition of JNK3 is a promising strategy for treatment of neurodegeneration. The optimization of aminopyrazole-based JNK3 inhibitors with improved potency, isoform selectivity, and pharmacological properties by structure-activity relationship (SAR) studies utilizing biochemical and cell-based assays, and structure-based drug design is reported. These inhibitors had high selectivity over JNK1 and p38α, minimal cytotoxicity, potent inhibition of 6-OHDA-induced mitochondrial membrane potential dissipation and ROS generation, and good drug metabolism and pharmacokinetic (DMPK) properties for iv dosing. 26n was profiled against 464 kinases and was found to be highly selective hitting only seven kinases with >80% inhibition at 10 μM. Moreover, 26n showed good solubility, good brain penetration, and good DMPK properties. Finally, the crystal structure of 26k in complex with JNK3 was solved at 1.8 ? to explore the binding mode of aminopyrazole based JNK3 inhibitors.
STUDIES IN THE FIELD OF NITROGEN HETEROCYCLIC COMPOUNDS. PART X. SYNTHESIS AND NEW RING TRANSFORMATION OF SOME FUSED PYRAZOLE SYSTEMS
Balicki, Roman
, p. 1273 - 1278 (2007/10/02)
Condensation of 3-amino-1-methylpyrazole (7) with ethyl acetoacetate (1) in ethanol leads to formation of aminocrotonate 8, whereas the reaction in Dowtherm A above 200 deg C gives acetoacetamide (9).Ring closure of 8 in polyphosphoric acid (PPA) or ethanolic hydrochloride gives pyrazolopyrimidine (10).However, in Dowtherm A besides compound 10, the pyrazolopyridine (11) is also formed.Heating of 10 in Dowtherm A at 220-240 deg C causes ring transformation into 11.In acetic acid, compound 8 undergoes rearrangement to acetoacetamide 9 prior to cyclization into pyrazolopyridine (12).The structures of the compounds obtained were deduced from their IR, MS, 1H NMR and 13C NMR spectra.Pathways of the reactions presented are also discussed.
