Antihypertensive and Cardiovascular Effects of a New Potassium Channel Opener, TCV-295, in Rats and Dogs

Kusumoto, Keiji; Awane, Yumiko; Kitayoshi, Takahito; Fujiwara, Shuji; Hashiguchi, Shouhei; Terashita, Zen‐ichi; Shiraishi, Masayuki; Watanabe, Toshifumi

doi:10.1097/00005344-199424060-00010

Cited by 11 publications

(4 citation statements)

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“…The decrease in A-V O 2 caused by JTV-506 may be attributed to an increase in CBF and a reduction of afterload accompanied with slight hypotension. Similar changes in A-V O 2 have already been reported when the potassium channel openers, KRN2391 and TCV-295 were administered to anesthetized dogs [7,8]. JTV-506 increased subendocardial PO 2 dose dependently and showed a tendency to decrease MBP and increase LV dP/dt max, but had almost no effect on HR and LVEDP.…”

Section: Discussionsupporting

confidence: 78%

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

Hirata

Suzuki

Miyai

et al. 2011

Arzneimittelforschung

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The effects of JTV-506 ((-)-(3S,4R)-2,2-bis(methoxymethyl)-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)amino]-3-hydroxychroman-6-carbonitrile hemihydrate, CAS 170148-29-5), a novel coronary vasodilator, on hemodynamics, cardiac function and cardiac oxygen consumption were evaluated in anesthetized dogs. In anesthetized, open-chest dogs, JTV-506 (0.3-10 micrograms/kg i.v.) induced a marked increase in coronary blood flow in a dose dependent manner, while at these doses it had smaller effects on vertebral and mesenteric blood flow and almost no effect on renal blood flow. JTV-506 (1-10 micrograms/kg i.v.) showed a tendency to decrease oxygen consumption of the heart and elevate myocardial oxygen pressure without cardiac suppression. Effects of JTV-506 on hemodynamics and the respiratory system following i.v. administration (0.3-300 micrograms/kg) were investigated in spontaneously breathing anesthetized dogs. The effective dose to induce hemodynamic changes was more than 3 micrograms/kg. JTV-506 did not have a crucial influence on electrocardiogram. JTV-506 caused marked increase in coronary blood flow and myocardial oxygen pressure with slight change in blood pressure. It is concluded that JTV-506 is a potent vasodilator, with particularly pronounced effect on vasculature of the heart. These results suggest that JTV-506 may be useful in the treatment of angina pectoris.

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Section: Discussionsupporting

confidence: 78%

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

Hirata

Suzuki

Miyai

et al. 2011

Arzneimittelforschung

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“…In conscious, spontaneously hypertensive rats (SHR), TCV-295, reduced blood pressure (BP) with low dose dependently and with slow onset of action were observed. 152 An efficient process for potassium channel opener, TCV-295, based on a 4-(2-pyridyl) -2H-1,3-benzoxazine ring formation from o-hydroxybenzoylpyridine by the NH4I/piperidine/2,2-dimethoxypropane system and the following selective pyridine-N-oxidation using dimethyldioxirane, has been examined. 153 In addition, a series of 1, 3-benzoxazine derivatives with a 2-pyridine-1oxide group at C4 (12) was synthesized to explore K + channel openers by onepot 1, 3-benzoxazine skeleton formation using a palladium (0)-catalyzed carbon-carbon bond formation reaction of imino-triflates with organozinc reagents.…”

Section: Antihypertinsive Activitiesmentioning

confidence: 99%

3,4-Dihydro-2H-1,3-benzoxazines and their oxo-derivatives - Chemistry and bioactivities

Eldin

2021

JSCS

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It must be stressed that the manuscript still has to be subjected to copyediting, typesetting, English grammar and syntax corrections, professional editing and authors' review of the galley proof before it is published in its final form. Please note that during these publishing processes, many errors may emerge which could affect the final content of the manuscript and all legal disclaimers applied according to the policies of the Journal.

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“…In particular, compound TCV-295 (49) showed the highest vasorelaxant activity in vitro with EC 50 = 0.14 µM which is 12-times more potent than CRK (EC 50 = 1.8 µM). After oral administration in SHR and normotensive dogs, TCV-295 (49) induced a long-lasting hypotensive effect superior to that of CRK, LCRK and nisoldipine, and evoked less reflex tachycardia [86,87]. TCV-295 (49) ZM-260384 (50) As a part of a program aimed at finding K ATP COs for use in urinary incontinence, fluorinated 1,4-benzoxazine pyridine-N-oxides, typified by ZM-260384 (50), were developed at Zeneca [88; Fig.…”

Section: Benzoxazinesmentioning

confidence: 99%

From Cromakalim to Different Structural Classes of KATP Channel Openers

Cecchetti¹,

Tabarrini²,

Sabatini³

2006

CTMC

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ATP-Sensitive potassium channel openers (K(ATP)COs) are a group of compounds with a broad spectrum of potential therapeutic applications, as they constitute efficient tools for dampening cell excitability. Interest in the K(ATP)COs was triggered in the early 1980s by the discovery of the benzopyran-based structure cromakalim (CRK), which is a powerful smooth muscle relaxant. CRK can be considered the archetype of K(ATP)COs and is by far the most mimicked structure. In many structure-activity studies various substitutions have been made at the different positions of the benzopyran ring permitting the optimal activity to be correlated with a specific set of structural characteristics and stereochemical features of the molecule. Thus, many potent benzopyran derivatives have been identified. The benzopyran nucleus itself has also been modified in both the aromatic ring and in the pyran moiety. The intention of this review is to bring together all the different structural classes of K(ATP)COs arising from the replacement of CRK benzopyran-based structure with various ring systems; design, structure-activity relationship, and synthesis will be given.

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Antihypertensive and Cardiovascular Effects of a New Potassium Channel Opener, TCV-295, in Rats and Dogs

Cited by 11 publications

References 0 publications

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

3,4-Dihydro-2H-1,3-benzoxazines and their oxo-derivatives - Chemistry and bioactivities

From Cromakalim to Different Structural Classes of KATP Channel Openers

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