Cardiotonic agents. 5. Fragments from the heterocycle-phenyl-imidazole pharmacophore

Erhardt, Paul; Hagedorn, Alfred A.; Davey, David D.; Pease, Cynthia A.; Venepalli, Bhaskar R.; Griffin, Carl W.; Gomez, Robert; Wiggins, Jay R.; Ingebretsen, W. R.

doi:10.1021/jm00126a005

Cited by 25 publications

(12 citation statements)

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“…Thus, CK-2289 is a direct acting, positive inotropic agent in the pentobarbital-anesthetized dog. Similar conclusions can be reached for milrinone and enoxi- [Weishaar et al, 1985a[Weishaar et al, ,b, 1986aAlousi and Johnson, 1986;Erhardt et al, 1989;Harris et al, 19891. CK-2289, milrinone, and enoximone inhibit type I11 cyclic adenosine monophosphate (CAMP) phosphodiesterase (PDE) obtained from canine, guinea pig, and ferret heart and vascular smooth muscle, in vitro [Weishaar et al, 1985a[Weishaar et al, ,b, 1986a[Weishaar et al, ,b, 1987Ahn et al, 1986;Alousi and Johnson, 1986;Earl et al, 1986a;Erhardt et al, 1989;Harris et al, 19891 and CAMP-dependent protein kinase [Earl et al, 1986bl.…”

Section: Discussionsupporting

confidence: 60%

“…Inhibition of cAMP PDE may also account for the vasodilator and positive chronotropic effects of CK-2289, milrinone, and enoximone. The relative potencies of milrinone and other compounds as inhibitors of cardiac and vascular smooth muscle cAMP PDE differ [Weishaar et al, 1985a[Weishaar et al, ,b, 1986aErhardt et al, 1989;Harris et al, 19891. This may reflect the 1) different isomeric forms of cAMP PDE in cardiac and smooth muscle, and 2) similarities between the compounds as positive inotropes despite the differences in relative potency as vasodilator agents.…”

Section: Discussionmentioning

confidence: 99%

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Hemodynamic profile of the new cardiotonic agent CK‐2289 compared to milrinone and enoximone in the anesthetized dog

Greenberg

Paul

Touhey

1991

Drug Development Research

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Greenberg, S.S., J. Paul, and B. Touhey: Hemodynamic profile of the new cardiotonic agent CK-2289 compared to milrinone and enoximone in the anesthetized dog. Drug Dev. Res. 23:109-126. 1991. We examined the hemodynamic profile of CK-2289, a new imidazolone developed for the treatment of congestive heart failure, in the normal pentobarbital-anesthetized dog. Mongrel dogs (10-18 kg) of either sex were anesthetized with pentobarbital sodium (35 mgikg, intravenously [i.v.]) and instrumented for routine hemodynamic measurements using an open-chest, artificially ventilated preparation. Intravenous administration of CK-2289 (3, 10, 30, and 100 pg/kg) to pentobarbital-anesthetized dogs increased left ventricular (LV) dP/ d T , , by 9, 26, 73, and 80%, respectively, and decreased mean arterial pressure (MAP) by 2, 6, 18, and 34%. CK-2289 was 2.7 times more potent as a positive inotropic agent than as a vasodilator. Heart rate (HR) increased by 2, 10, 18, and 28% after these doses of CK-2289, while left ventricular end diastolic pressure (LVEDP) decreased by 4.5 mmHg after the highest dose of compound. CK-2289 increased coronary blood flow (CBF) after each dose of compound. However, the increased CBF was less than that produced by milrinone for equivalent increases in LV dP/ dT, , , .Renal blood flow increased while vertebral blood flow was reduced after administration of the two highest doses of CK-2289. However, vertebral vascular resistance decreased slightly from control values. Milrinone and enoximone behaved qualitatively similar to, but were 6 and 27 times less potent than

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Hemodynamic profile of the new cardiotonic agent CK‐2289 compared to milrinone and enoximone in the anesthetized dog

Greenberg

Paul

Touhey

1991

Drug Development Research

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“…Imidazole is of great significance as a ligand due to its presence in many biological systems (such as amino acids histidine and purines, enzymes) and providing a potential binding site for metal ions (Edsall et al, 1954;Brooks andDavidson 1960, Mighell andSantoro, 1971). Imidazole and its derivatives have become an important part of many pharmacological activities such as, analgesic, anti-inflammatory (Suzuki et al, 1992), anti-anthelmintic (Lunt et al, 1987), anti-fungal (Johnson et al, 1999), antitubercular (Pandey et al, 2009), antimicrobial (Vijesh et al, 2013), anticancer (Miyachi et al, 1998) and cardiovascular (Erhardt et al, 1989) activities. Except their pharmacological effects, they also function as catalysts (Jencks, 1970) and polymerizing agents (Samdal and Møllendal, 2011) for example 1vinylimidazole (vim) ( Figure 1) is used as a copolymerization agent in the production of cationic polymers (Ebel et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Cadmium(II) Chloride Complex Containing 1-Vinylimidazole Ligand: Structural, Spectroscopic and Thermal Properties

Yolcu

2020

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi

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In this work dichlorotetrakis(1-vinylimidazole)cadmium(II), [CdCl2(vim)4] complex was synthesized using 1vinylimidazole (vim) ligand and CdCl2. The structure of the complex was characterized by FT-IR spectroscopy, thermal analysis (TG, DTG, DTA) and X-ray single crystal studies. In the FT-IR spectrum of the complex, the characteristic peaks (C−H stretch, C=C and C=N vibration bands) of vim were observed. X-ray crystallographic data of the titled complex revealed that vim ligand coordinated to the metal atom via the heterocyclic ring nitrogen atom. The coordination geometry of the Cd(II) central atom is elongated octahedral. Compound crystallized in P21/n space group, and the mononuclear units were weakly linked to each other by C-H⋯Cl hydrogen bonds. It was determined by thermal analysis data that the complex degraded in four steps and total mass loss was 99%.

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“…The N-arylazoles and biarylethers are among the most commonly found motifs in pharmaceuticals, biologically active molecules, crop-protection chemicals, and material science. A huge number of drugs contain N-arylimidazole moieties including cyclic AMP phosphodiesterase inhibitors (Sircar et al, 1987; Venuti et al, 1988; Güngör et al, 1992; Martinez et al, 1992; Sawanishi et al, 1997), thromboxane synthase inhibitors (Iizuka et al, 1981; Martinez et al, 1992; Cozzi et al, 1993; Nicolaï et al, 1993), topical antiglaucoma agents (Lo et al, 1992), and cardiotonic agents (Hagedorn et al, 1987; Erhardt et al, 1989; Shaw et al, 1992). In this regard, transition-metal catalyzed C-heteroatom coupling reactions have become one of the most important areas in modern chemical synthesis.…”

Section: Introductionmentioning

confidence: 99%

C−X (X = N, O) Cross-Coupling Reactions Catalyzed by Copper-Pincer Bis(N-Heterocyclic Carbene) Complexes

et al. 2019

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Over the last two decades, N-heterocyclic carbene (NHC)–copper catalysts have received considerable attention in organic synthesis. Despite the popularity of copper complexes containing monodentate NHC ligands and recent development of poly(NHC) platforms, their application in C–C and C–heteroatom cross-coupling reactions has been limited. Recently, we reported an air-assisted Sonogashira-type cross-coupling catalyzed by well-defined cationic copper-pincer bis(NHC) complexes. Herein, we report the application of these complexes in Ullmann-type C–X (X = N, O) coupling of azoles and phenols with aryl halides in a relatively short reaction time. In contrast to other well-defined copper(I) catalysts that require an inert atmosphere for an efficient C–X coupling, the employed Cu(I)-pincer bis(NHC) complexes provide good to excellent yields in air. The air-assisted reactivity, unlike that in the Sonogashira reaction, is also affected by the base employed and the reaction time. With Cs2CO3 and K2CO3, the oxygen-generated catalyst is more reactive than the catalyst formed under argon in a short reaction time (12 h). However, the difference in reactivity is compromised after a 24 h reaction with K2CO3. The efficient pincer Cu-NHC/O2/Cs2CO3 system provides great to excellent cross-coupling yields for electronically diverse aryl iodides and imidazole derivatives. The catalyst scope is controlled by a balance between nucleophilicity, coordinating ability, and the steric hindrance of aryl halides and N-/O-nucleophiles.

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Cardiotonic agents. 5. Fragments from the heterocycle-phenyl-imidazole pharmacophore

Cited by 25 publications

References 1 publication

Hemodynamic profile of the new cardiotonic agent CK‐2289 compared to milrinone and enoximone in the anesthetized dog

Hemodynamic profile of the new cardiotonic agent CK‐2289 compared to milrinone and enoximone in the anesthetized dog

Cadmium(II) Chloride Complex Containing 1-Vinylimidazole Ligand: Structural, Spectroscopic and Thermal Properties

C−X (X = N, O) Cross-Coupling Reactions Catalyzed by Copper-Pincer Bis(N-Heterocyclic Carbene) Complexes

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