138401-20-4Relevant academic research and scientific papers
Synthesis and screening for acetylcholinesterase inhibitor activity of some novel 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-ones: Derivatives of irbesartan key intermediate
Kavitha,Gaonkar,Narendra Sharath Chandra,Sadashiva,Rangappa
, p. 7391 - 7398 (2008/09/17)
The association of bioactive nucleus with other pharmacological agents is hoped to improve the efficacy of the treatment by combining the effects of different pharmacological mechanisms of action. Keeping this in view, a series of 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-one derivatives have been synthesized by interaction of 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-one with different bioactive aralkyl halides in presence of powdered potassium carbonate by two different methods viz., conventional and microwave irradiation. The yields under conventional and microwave irradiation methods were in the range of 60-65% and 80-90%, respectively. The structure elucidation of the new compounds has been carried out with the help of elemental analysis and spectral data. All the synthesized compounds have been screened for their efficacy as acetylcholinesterase (AChE) inhibitor. AChE inhibitory activity study was carried out by using Ellman colorimetric assay with neostigmine as a reference standard against targets from different species, such as pure electric eel AChE, human serum AChE, and rat brain AChE. Among the compounds synthesized, compounds 5a, 5b, 5j showed good inhibition against AChE.
A New Series of Imidazolones: Highly Specific and Potent Nonpeptide AT1 Angiotensin II Receptor Antagonists
Bernhart, Claude A.,Perreaut, Pierre M.,Ferrari, Bernard P.,Muneaux, Yvette A.,Assens, Jean-Louis A.,et al.
, p. 3371 - 3380 (2007/10/02)
Starting from the structure of the novel nonpeptide AT1 receptor antagonists DuP 753 (losartan), a new series of potent antagonists was designed.In these compounds the central imidazole nucleus was replaced by the dihydroimidazol-4-one structure.The most active compounds had a spirocyclopentane or a spirocyclohexane ring in position 5.Like the imidazole series, the best substituents were the linear butyl chain in position 2 and the methyl group in position 3.Antagonistic activity was assessed by the ability of the compounds to competively inhibit AII binding to the AT1 subtype receptor and to antagonize AII-induced contractions in rabbit aorta rings.The most active compounds had IC50 values in the nanomolar range.In conscious rats, compounds 4 and 21 antagonized the AII pressor response when administered orally.Compound 21 (SR 47436) was the most active; it was recently shown to also be active in cynomolgus monkeys both intravenously and orally.This molecule is now undergoing clinical trials for the treatment of hypertension.
