122689-91-2Relevant academic research and scientific papers
Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
, (2020/09/16)
To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
CYCLOPEPTIDE ALKALOID MODEL STUDIES. A TWO-STEP CONVERSION OF 5-AMINOISOXAZOLES TO AMINO ACID BIS-AMIDES
Lipshutz, Bruce H.,Reuter, Deborah C.
, p. 6067 - 6070 (2007/10/02)
Thermolyses of substituted 5-aminoisoxazoles, readily available from common starting materials, lead to azirines in good yields.Subsequent hydration affords bis-amide derivatives of amino acids.
