7-(Trifluoromethyl)-4-aminoquinoline hypotensives: novel peripheral sympatholytics

Abstract

A family of 7-(trifluoromethyl)-4-aminoquinolines that are hypotensive agents and that act by a novel sympatholytic mechanism is described. Structure-activity relationships in this series have been elucidated. Some of the more potent hypotensives were evaluated for safety in the mouse. A candidate, 1-[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4- quinolinyl]amino]benzoyl]piperazine hydrochloride (losulazine hydrochloride) has been selected for clinical development. Losulazine hydrochloride is a hypotensive agent in the rat, cat, and dog. At acute effective hypotensive doses, it does not block the response of the sympathetic nervous system to stimuli. Both animal pharmacology and clinical experience suggest that losulazine hydrochloride may be free of the clinically limiting side effects that often plague compounds that decrease blood pressure by interfering with autonomic neurogenic function.

Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities

“…Additionally, quinolines are considered as an interesting group of compounds, many of which have widespread pharmacologicalactions such as anti-microbial, [1][2][3][4] anti-inflammatory, [5][6][7][8] antitubercular, [9][10][11][12] anti-convulsant, [13] antihypertensive, [14,15] antioxidant, [16][17][18][19] and anticancer [20] activities. Nitrones can release nitric oxide in larger amounts compared to corresponding oximes.…”

“…actions such as anti-microbial, [1][2][3][4] anti-inflammatory, [5][6][7][8] antitubercular, [9][10][11][12] anti-convulsant, [13] antihypertensive, [14,15] antioxidant, [16][17][18][19] and anticancer [20] activities. Several mechanisms can explain the anticancer effect of quinoline derivatives including: topoisomerase inhibition, [21][22][23] DNA intercalation, [24] protein kinases inhibition, [25][26][27] tubulin polymerase inhibition, [28][29][30][31] and induction of apoptosis.…”

Pyridazinone: an important element of pharmacophore possessing broad spectrum of activity

“…A further research in this field in search of safer and more potent compounds led to the discovery of milrinone and its analogs (Bekhit and Baraka, 2005;Abadi et al, 1999). To develop SAR in the series, several pyridazinone derivatives of amrinone were also synthesized (Combs et al, 1992;Bakewell et al, 1990;McCall et al, 1986;Pastelin et al, 1983). Their mechanism of action was established, and a five-point model and pharmacophore were identified (Leclerc et al, 1986;Erhardt et al, 1988;Bristol et al, 1984).…”

N-[(2-Chloro-6-methylquinolin-3-yl)methyl]aniline

“…Quinolinyl amines are important organic compounds which possess a variety of pharmacological activities such as antimalarial, antifungal, hypotensive and antidepressant activity [1][2][3][4]. From the various conditions adopted for the synthesis of secondary amines reported in the literature, synthesis via nucleophilic substitution is still an important method [5].…”