Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

Gerspacher, Marc; Vecchia, Luigi La; Mah, Robert; Sprecher, Andreas von; Anderson, Gary P.; Subramanian, N.; Hauser, Kathleen; Bammerlin, Heinrich; Kimmel, S.; Pawelzik, Viviane; Ryffel, Karin; Ball, Howard

doi:10.1016/s0960-894x(01)00631-x

Cited by 17 publications

(8 citation statements)

References 13 publications

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“…DNK333 is a dual NK 1 /NK 2 tachykinin receptor antagonist. In ligand binding studies DNK333 binds to cloned human tachykinin NK 1 and NK 2 receptors with similar affinity (inhibitory concentration at 50% values 4.8 and 5.5 nM) [19]. At the start of our study the specificity of DNK333 for tachykinin receptors had been studied in vivo in animals and in vitro on human colonic mucosa cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, DNK333 inhibited bronchoconstriction induced by tachykinin NK 1 -and NK 2 -receptor agonists in guinea pigs and squirrel monkeys [19][20][21]. The present investigation utilised a randomised, double-blind, placebo-controlled, two-treatment crossover design to examine the effects of DNK333 on neurokinin A-induced bronchoconstriction in patients with asthma.…”

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confidence: 99%

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Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients

Joos¹,

Vincken²,

Louis³

et al. 2004

European Respiratory Journal

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Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK 1 and NK 2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK 1 /NK 2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma.A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled, crossover trial. Increasing concentrations of NKA (3.3610 -9 to 1.0610 -6 mol?mL -1 ) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo.It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log 10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log 10 mol?mL -1 at 1 h after DNK333 treatment and -6.8 log 10 mol?mL -1 after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment.The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma. Eur Respir J 2004; 23: 76-81.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients

Joos¹,

Vincken²,

Louis³

et al. 2004

European Respiratory Journal

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“…Some of the compounds were found to be more potent than nibentan and possessed a longer duration of action. The antifibrillatory activity of (±)-N-[5-(diethylamino)-1-(4-methoxyphenyl) pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-satalol and sematilide [34,35].…”

Section: Miscellaneousmentioning

confidence: 93%

Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry

Asif¹

2016

Mod Chem Appl

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Benzamide derivatives possess different kinds of pharmacological activities like antimicrobial, analgesic, antiinflammatory, anticancer, cardiovascular, and other biological activities. Due to these biologically significances, scientists have interesting to develop various new benzamide derivatives. There is still need to improve the already used benzamide derivatives and search for the new and more effective benzamide derivatives. This review exhibited various pharmacophoric activities of benzamides analogues which are biologically importance.

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“…DNK333, a novel drug that antagonises the NK 1 , NK 2 and NK 3 receptors, appears to be a candidate agent for use in IBS‐D 26, 27 . In preclinical studies, DNK333 has demonstrated the ability to normalise exaggerated motor and secretory function in the GI tract and to relieve abdominal pain/discomfort, without mediating changes in normal gut function (Data on file, Novartis).…”

Section: Introductionmentioning

confidence: 99%

Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome

Zakko¹,

Barton²,

Weber³

et al. 2011

Alimentary Pharmacology &Amp; Therapeutics

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Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

Cited by 17 publications

References 13 publications

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients

Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry

Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome

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