7461-50-9Relevant articles and documents
Synthesis method of imidazopyridine or pyrimidine derivative
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Paragraph 0037-0039, (2021/05/29)
The invention belongs to the technical field of synthesis, and particularly relates to a synthesis method of an imidazopyridine or pyrimidine derivative. The imidazopyridine or pyrimidine compound is obtained by taking pyridine or pyrimidinecarboxylic acid as a synthon through amidation, Hofmann degradation and cyclization reaction, and the obtained imidazopyridine or pyrimidine derivative can be further converted to generate a functional product. The method has the advantages of easily available raw materials, simple operation, high reaction efficiency, convenient post-treatment, and diversity of functional groups.
Synthesis and functional characterization of imbutamine analogs as histamine H3 and H4 receptor ligands
Geyer, Roland,Kaske, Melanie,Baumeister, Paul,Buschauer, Armin
, p. 77 - 88 (2014/03/21)
Imbutamine (4-(1H-imidazol-4-yl)butanamine) is a potent histamine H 3 (H3R) and H4 receptor (H4R) agonist (EC50 values: 3 and 66 nM, respectively). Aiming at improved selectivity for the H4R, the imidazole ring in imbutamine was methyl-substituted or replaced by various differently substituted heterocycles (1,2,3-triazoles, 1,2,4-triazoles, pyridines, pyrimidines) as potential bioisosteres. Investigations in [35S]GTPγS binding assays using membranes of Sf9 insect cells expressing the respective human histamine receptor subtype revealed only very weak activity of most of the synthesized hetarylalkylamines at both receptors. By contrast, the introduction of substituents at the 4-imidazolyl ring was most effective regarding H 4R selectivity. This holds for methyl substitution in position 2 and, especially, in position 5. 5-Methylimbutamine (H4R: EC50 = 59 nM, α = 0.8) was equipotent with imbutamine at the hH4R, but revealed about 16-fold selectivity for the hH4R compared to the hH3R (EC50 980 nM, α = 0.36), whereas imbutamine preferred the hH3R. The functional activities were in agreement with radioligand binding data. The results support the hypothesis that, by analogy with histamine, methyl substitution in histamine homologs offers a way to shift the selectivity in favor of the H4R. According to a bioisosteric approach, the imidazole ring in the dual histamine H3/H4 receptor agonist imbutamine (n = 4) was replaced by various five- and six-membered N-heterocycles. Whereas these structural modifications resulted in a reduction or loss of activity at both receptors, 5-methyl substitution at the imidazol-4-yl ring in imbutamine changed the receptor subtype selectivity in favor of the H4R.
NEW BRADYKININ B1 ANTAGONISTS
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Page/Page column 62, (2010/04/03)
The invention relates to compounds of formula (I) where in R1, R1a, R1b, R2, R3 and X, X1, X2, X3 have the meaning as cited in the description and the claims. Said compounds are useful as Bradykinin B1 antagonists. The invention also relates to pharmaceutical compositions, the preparation of such compounds as well as the production and use as medicament.
