A series of methylpiperidinyl phenols, methylphenylmorpholinyl phenols and methylthiophenylmorpholinyl phenols were synthesized in one-pot transformation by Mannich reactions using infrared irradiation under solvent-free conditions. The chemical structures of the compounds were proved by IR, 1 H NMR, 13 C NMR and MS spectroscopic data.
Antihypertensive activity X 0120Synthesis and Antihypertensive Effects of New Methylthiomorpholinphenol Derivatives. -The novel compounds (I) are evaluated for their antihypertensive activity. The results are discussed in detail in comparison with other cardiovascular drugs such as captopril, losartan and omapatrilat. LQM303 (Ic) exhibits the best decreasing effect in both systolic and diastolic pressure and the best heart rate decreasing effect. -(VELAZQUEZ, A. M.; MARTINEZ, L.; ABREGO, V.; BALBOA, M. A.; TORRES, L. A.; CAMACHO, B.; DIAZ-BARRIGA, S.; ROMERO, A.; LOPEZ--CASTANARES, R.; ANGELES*, E.; Eur.
A main target in the treatment of hypertension is the angiotensin-converting enzyme (ACE). This enzyme is responsible for producing angiotensin II, a potent vasoconstrictor. Therefore, one of the targets in the treatment of hypertension is to inhibit ACE activity. Hence, this study’s aim is to use computational studies to demonstrate that the proposed heterocyclic compounds have a molecular affinity for ACE and that, furthermore, these heterocyclic compounds are capable of inhibiting ACE activity, thus avoiding the production of the vasopressor Angiotensin II. All this using computer-aided drug design, and studying the systems, with the proposed compounds, through molecular recognition process and compared with the compounds already on the market for hypertension.
Four new antihypertensive thiomorpholinylmethylphenol compounds were synthesized by its potential antihypertensive and antiarhythmic properties. The pK a values were determined experimentally, with the aid of program SQUAD, by Capillary Zone Electrophoresis (CZE) (T ) 310.15 K and I ) 0.05 mol • dm -3 ) and by UV spectrophotometry at pseudophysiological conditions (T ) 310.15 K and I ) 0.15 mol • dm -3 ), obtaining good agreement between the values determined with both techniques. A theoretical study was followed to propose a deprotonation mechanism for each compound. The log P values were also determined between n-octanol and water and compared with the values of other similar compounds to relate it with its possible biological activity.
The balance between cell proliferation and cell growth characterizes tissue homeostasis on one side and cell death on the other side. Fas receptor-mediated apoptosis is a control mechanism for tissue homeostasis, and avoiding this death pathway predisposes to many human diseases, including cancer. Current therapies for this disease are invasive and do not have the desired effect in the control of the disease. In this context, the search for new drugs that contribute to a better treatment is gaining more relevance. 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol (LQM319) [1,2] is a drug currently in preclinical stage, and we have shown that it has a hypertensive effect, similar to captopril, in a hypertensive rat model. Different studies have shown that some chemicals that are used as antihypertensive agents have an antineoplastic effect against certain types of cancer, as is the case of hydralazine [3], and captopril [4], among others [5]. On the other hand, it has been reported that morpholine derivatives may activate Fas (CD95)-mediated apoptosis. The aim of the present study was to show the interaction between CD95 (receptor) and thiomorpholine derivatives (ligand) using molecular modeling and docking studies, and to elucidate the possible action mechanism of 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol.
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